Is STRC p.Trp862Cys (c.2586G>T) pathogenic?

STRC p.Trp862Cys (c.2586G>T) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely pathogenic (0.9852); Very rare (popmax 0.000526%, nfe); Associated with STRC-related disorder.

What condition is associated with STRC p.Trp862Cys (c.2586G>T)?

STRC p.Trp862Cys (c.2586G>T) is associated with STRC-related disorder (ClinVar).

How common is STRC p.Trp862Cys (c.2586G>T) in the general population?

STRC p.Trp862Cys (c.2586G>T) is very rare (popmax 0.000526%, nfe) (gnomAD).

What do computational predictors say about STRC p.Trp862Cys (c.2586G>T)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

STRC p.Trp862Cys

c.2586G>T · rs2507594035 · VCV2632736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000526%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

STRC-related disorder

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic · top 1% in STRC
REVEL	0.641	indeterminate
SaProt	LLR -14.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	28.4	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

Grpmax group 0.000526% European (non-Finnish) · 1/190,178 alleles

Overall 0.000316% 1/316,930 alleles · very rare exomes 1/297,368 · genomes 0/19,562 · 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.Trp862Cys
Coding: c.2586G>T
MANE Select: NM_153700
dbSNP: rs2507594035
Type: single nucleotide variant
Location: chr15:43613126 (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

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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-trp862cys (accessed [today's date]).

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