SFT2D2

Chr 1

SFT2 domain containing 2

Also known as: UNQ512, dJ747L4.C1.2

NCBI Gene: 375035 ENSG00000213064 UniProt: O95562

SFT2D2 encodes a protein that facilitates fusion of retrograde transport vesicles from endocytic compartments with the Golgi complex. The gene shows low constraint against loss-of-function variants (pLI = 0.01, LOEUF = 0.9), and no established disease associations have been reported to date.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in protein transport and vesicle-mediated transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.90

Clinical Summary— SFT2D2

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

22 VUS of 37 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?

0.90LOEUF

pLI 0.011

Z-score 1.81

OE 0.43 (0.22–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.16Z-score

OE missense 1.05 (0.88–1.25)

88 obs / 83.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.43 (0.22–0.90)

0≤0.351.4

Missense OE?1.05 (0.88–1.25)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 5 / 11.7Missense obs/exp: 88 / 83.8Syn Z: -0.03

This gene — mechanism propensity

0.84top 10%

GOF

0.79top 25%

LOF

0.1895th %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

37 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

Likely Benign1

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	22	22
Likely Benign	1	1
Benign	0	0
Total	23	23

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap SFT2D2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →