SPRR2F

Chr 1

small proline rich protein 2F

NCBI Gene: 6705 ENSG00000244094 UniProt: Q96RM1

Predicted to be involved in keratinocyte differentiation. Predicted to act upstream of or within response to estradiol. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.90

Clinical Summary— SPRR2F

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Population Constraint (gnomAD)

Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

11 VUS of 14 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.90LOEUF

pLI 0.085

Z-score -0.14

OE 1.16 (0.28–1.90)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.17Z-score

OE missense 1.08 (0.84–1.40)

41 obs / 38.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.16 (0.28–1.90)

0≤0.351.4

Missense OE?1.08 (0.84–1.40)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 1 / 0.9Missense obs/exp: 41 / 38.0Syn Z: -1.12

This gene — mechanism propensity

0.88top 5%

GOF

0.6444th %ile

LOF

0.2679th %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

14 submitted variants in ClinVar

ClinVar

Classification Summary

VUS11

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	11	11
Likely Benign	2	2
Benign	0	0
Total	13	13

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap SPRR2F — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →