Is STRC p.Cys1491Phe (c.4472G>T) pathogenic?

STRC p.Cys1491Phe (c.4472G>T) is classified Conflicting classifications of pathogenicity in STRC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-02-26). AlphaMissense: likely pathogenic (0.9515); Very rare (popmax 0.000932%, nfe); Associated with STRC-related disorder.

What condition is associated with STRC p.Cys1491Phe (c.4472G>T)?

STRC p.Cys1491Phe (c.4472G>T) is associated with STRC-related disorder (ClinVar).

How common is STRC p.Cys1491Phe (c.4472G>T) in the general population?

STRC p.Cys1491Phe (c.4472G>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about STRC p.Cys1491Phe (c.4472G>T)?

AlphaMissense predicts likely pathogenic (score 0.9515) — an in-silico prediction, not a clinical call.

STRC p.Cys1491Phe

c.4472G>T · rs1482623890 · VCV805530

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STRC-related disorder

Computational evidence

Protein change
AlphaMissense	0.9515	likely pathogenic · top 3% in STRC
REVEL	0.652	pathogenic-leaning
SaProt	LLR -11.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,913 bp · p 0.26 · regional, not allelic
Overall
CADD	23.1	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 0.000932% European (non-Finnish) · 11/1,179,890 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,872 alleles · very rare exomes 11/1,461,702 · genomes 0/152,170 · joint denominator

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.Cys1491Phe
Coding: c.4472G>T
MANE Select: NM_153700
dbSNP: rs1482623890
Type: single nucleotide variant
Location: chr15:43603315 (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

STRC-related disorder

Similar variants

STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1073Ter Pathogenic ★★ same condition
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1729Ter Pathogenic ★★ same condition
STRC p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Gln1343Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Gln1353Ter Pathogenic ★★ same condition
STRC p.Trp1475Cys Pathogenic/Likely pathogenic ★★ ⚠ 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-cys1491phe (accessed [today's date]).

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