Is STRC p.Cys485Phe (c.1454G>T) pathogenic?

STRC p.Cys485Phe (c.1454G>T) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-13). AlphaMissense: likely pathogenic (0.9065); Absent from gnomAD v4.1.

How common is STRC p.Cys485Phe (c.1454G>T) in the general population?

STRC p.Cys485Phe (c.1454G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STRC p.Cys485Phe (c.1454G>T)?

AlphaMissense predicts likely pathogenic (score 0.9065) — an in-silico prediction, not a clinical call.

STRC p.Cys485Phe

c.1454G>T · rs2507595825 · VCV3075828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9065 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9065	likely pathogenic · top 6% in STRC
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -10.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 0.82, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STRC
Protein: p.Cys485Phe
Coding: c.1454G>T
MANE Select: NM_153700
dbSNP: rs2507595825
Type: single nucleotide variant
Location: chr15:43616112 (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

Similar variants

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STRC p.Arg1154Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1224Ter Pathogenic ★★ same type
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1451Ter Pathogenic/Likely pathogenic ★★ same type
STRC p.Arg1468Ter Pathogenic ★★ 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/strc-p-cys485phe (accessed [today's date]).

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