Is STRC p.Val294Ile (c.880G>A) pathogenic?

STRC p.Val294Ile (c.880G>A) is classified Benign in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2013-10-05). AlphaMissense: likely benign (0.0673); Very rare (popmax 0.00636%, sas).

How common is STRC p.Val294Ile (c.880G>A) in the general population?

STRC p.Val294Ile (c.880G>A) is very rare (popmax 0.00636%, sas) (gnomAD).

What do computational predictors say about STRC p.Val294Ile (c.880G>A)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

STRC p.Val294Ile

c.880G>A · rs727503451 · VCV165322

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP -3.7
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	0.084	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00636% South Asian · 3/47,202 alleles

Filtering AF 0.00169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00115%

Overall 0.00294% 15/509,438 alleles · very rare exomes 11/399,846 · genomes 4/109,592 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00636%	15,734
Admixed American	0.00358%	27,898
East Asian	0.00321%	31,134
European (non-Finnish)	0.00308%	32,508
African / African-American	0.0028%	35,730

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.Val294Ile
Coding: c.880G>A
MANE Select: NM_153700
dbSNP: rs727503451
Type: single nucleotide variant
Location: chr15:43616686 (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-val294ile (accessed [today's date]).

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