Is STRC p.Arg832Trp (c.2494C>T) pathogenic?

STRC p.Arg832Trp (c.2494C>T) is classified Uncertain significance in STRC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-21). AlphaMissense: ambiguous (0.3754); Ultra-rare (popmax 0.0253%, amr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Arg832Trp (c.2494C>T)?

STRC p.Arg832Trp (c.2494C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Arg832Trp (c.2494C>T) in the general population?

STRC p.Arg832Trp (c.2494C>T) is ultra-rare (popmax 0.0253%, amr) (gnomAD).

What do computational predictors say about STRC p.Arg832Trp (c.2494C>T)?

AlphaMissense predicts ambiguous (score 0.3754) — an in-silico prediction, not a clinical call.

STRC p.Arg832Trp

c.2494C>T · rs876658007 · VCV229276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3754 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3754	ambiguous
REVEL	0.626	indeterminate
SaProt	LLR -5.49	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	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	28.3	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 0.0253% Admixed American · 5/19,758 alleles

Filtering AF 0.00993% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00644%

Overall 0.00445% 14/314,668 alleles · ultra-rare exomes 12/267,192 · genomes 2/47,476 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0253%	3,952
Remaining individualsnot grpmax-eligible	0.0152%	6,566
European (non-Finnish)	0.00372%	26,877

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.Arg832Trp
Coding: c.2494C>T
MANE Select: NM_153700
dbSNP: rs876658007
Type: single nucleotide variant
Location: chr15:43613218 (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 p.Arg832Gln Uncertain significance ★ ⚠ same residue
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.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-arg832trp (accessed [today's date]).

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