SFT2D1

Chr 6

SFT2 domain containing 1

Also known as: C6orf83, pRGR1

NCBI Gene: 113402 ENSG00000198818 UniProt: Q8WV19

The protein is predicted to be involved in vesicular transport between endocytic compartments and the Golgi complex. The gene shows low constraint against loss-of-function variants (pLI = 0.002, LOEUF = 1.07), and no established human disease associations have been reported to date.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in protein transport and vesicle-mediated transport. Predicted to be located in several cellular components, including cytoplasm; endomembrane system; and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.06

Clinical Summary— SFT2D1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

18 VUS of 42 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.06LOEUF

pLI 0.002

Z-score 1.42

OE 0.54 (0.29–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.31Z-score

OE missense 0.90 (0.74–1.10)

72 obs / 79.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.29–1.06)

0≤0.351.4

Missense OE?0.90 (0.74–1.10)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 6 / 11.1Missense obs/exp: 72 / 79.9Syn Z: -0.60

This gene — mechanism propensity

0.81top 10%

GOF

0.73top 25%

LOF

0.2190th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

42 submitted variants in ClinVar

ClinVar

Classification Summary

VUS18

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	18	18
Likely Benign	2	2
Benign	0	0
Total	20	20

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

52 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap SFT2D1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →