Is STRC p.Ala304Val (c.911C>T) pathogenic?

STRC p.Ala304Val (c.911C>T) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2014-01-03). AlphaMissense: likely benign (0.1755); Rare (popmax 0.145%, eas).

How common is STRC p.Ala304Val (c.911C>T) in the general population?

STRC p.Ala304Val (c.911C>T) is rare (popmax 0.145%, eas) (gnomAD).

What do computational predictors say about STRC p.Ala304Val (c.911C>T)?

AlphaMissense predicts likely benign (score 0.1755) — an in-silico prediction, not a clinical call.

STRC p.Ala304Val

c.911C>T · rs727503448 · VCV165319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1755 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1755	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.7	GERP 0.89, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	25.6	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 0.145% East Asian · 48/33,040 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.013% 67/516,424 alleles · rare exomes 65/429,932 · genomes 2/86,492 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.145%	688
South Asian	0.00641%	15,607
European (non-Finnish)	0.0053%	18,854

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: STRC
Protein: p.Ala304Val
Coding: c.911C>T
MANE Select: NM_153700
dbSNP: rs727503448
Type: single nucleotide variant
Location: chr15:43616655 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.21

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

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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/strc-p-ala304val (accessed [today's date]).

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