Is SRR p.Ser337Phe (c.1010C>T) pathogenic?

SRR p.Ser337Phe (c.1010C>T) is classified Uncertain significance in SRR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1165); Ultra-rare (popmax 0.068%, afr).

How common is SRR p.Ser337Phe (c.1010C>T) in the general population?

SRR p.Ser337Phe (c.1010C>T) is ultra-rare (popmax 0.068%, afr) (gnomAD).

What do computational predictors say about SRR p.Ser337Phe (c.1010C>T)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

SRR p.Ser337Phe

c.1010C>T · rs201876645 · VCV2462569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.068%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -1.5, phastCons 0.069
Regional constraint	o/e 0.92	unconstrained · MANE · 8,309 bp · p 0.12 · regional, not allelic
Overall
CADD	14.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.068% African / African-American · 51/75,044 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00341% 55/1,613,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.068%	1,471
Remaining individualsnot grpmax-eligible	0.0048%	20,834
European (non-Finnish)	8.48e-05%	1,179,917

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SRR
Protein: p.Ser337Phe
Coding: c.1010C>T
MANE Select: NM_021947
dbSNP: rs201876645
Type: single nucleotide variant
Location: chr17:2323860 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 11 PDB

Full SRR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRR p.Ala167Thr Uncertain significance ★ ⚠ same type
SRR p.Arg58His Uncertain significance ★ ⚠ same type
SRR p.Arg58Pro Uncertain significance ★ ⚠ same type
SRR p.Asp257Asn Uncertain significance ★ ⚠ same type
SRR p.Asp258Gly Uncertain significance ★ ⚠ same type
SRR p.Gln296Glu Uncertain significance ★ ⚠ same type
SRR p.Gln296His Uncertain significance ★ ⚠ same type
SRR p.Glu304Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/srr-p-ser337phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown