Is STRC p.Val1386Ala (c.4157T>C) pathogenic?

STRC p.Val1386Ala (c.4157T>C) is classified Conflicting classifications of pathogenicity in STRC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.285); Rare (popmax 0.735%, amr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Val1386Ala (c.4157T>C)?

STRC p.Val1386Ala (c.4157T>C) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Val1386Ala (c.4157T>C) in the general population?

STRC p.Val1386Ala (c.4157T>C) is rare (popmax 0.735%, amr) (gnomAD).

What do computational predictors say about STRC p.Val1386Ala (c.4157T>C)?

AlphaMissense predicts likely benign (score 0.285) — an in-silico prediction, not a clinical call.

STRC p.Val1386Ala

c.4157T>C · rs377674360 · VCV227967

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.285 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.735%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.285	likely benign
REVEL	0.438	indeterminate
SaProt	LLR -8.27	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 9.2	GERP 2, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 3,913 bp · p 0.26 · regional, not allelic
Overall
CADD	22.6	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 0.735% Admixed American · 413/56,156 alleles

Filtering AF 0.677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.654%

Overall 0.0401% 635/1,584,908 alleles · rare exomes 507/1,433,162 · genomes 128/151,746 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.735%	136
East Asian	0.253%	395
Remaining individualsnot grpmax-eligible	0.0669%	1,495
African / African-American	0.0565%	1,771
Middle Eastern	0.0168%	5,948
South Asian	0.00453%	22,095
European (non-Finnish)	0.00189%	52,837

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.Val1386Ala
Coding: c.4157T>C
MANE Select: NM_153700
dbSNP: rs377674360
Type: single nucleotide variant
Location: chr15:43604422 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1102Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg1237Trp Uncertain significance ★★ ⚠ same condition
STRC p.Arg1338Gln Uncertain significance ★★ ⚠ same condition
STRC p.Arg56His Uncertain significance ★★ ⚠ same condition
STRC p.Arg832Trp Uncertain significance ★★ same condition
STRC p.Arg92Gln Uncertain significance ★★ ⚠ same condition
STRC p.Cys1464Tyr Uncertain significance ★★ ⚠ same condition

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-val1386ala (accessed [today's date]).

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