Is STRC p.Cys161Trp (c.483C>G) pathogenic?

STRC p.Cys161Trp (c.483C>G) is classified Uncertain significance in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely pathogenic (0.9003); Ultra-rare (popmax 0.028%, afr); Associated with Inborn genetic diseases.

What condition is associated with STRC p.Cys161Trp (c.483C>G)?

STRC p.Cys161Trp (c.483C>G) is associated with Inborn genetic diseases (ClinVar).

How common is STRC p.Cys161Trp (c.483C>G) in the general population?

STRC p.Cys161Trp (c.483C>G) is ultra-rare (popmax 0.028%, afr) (gnomAD).

What do computational predictors say about STRC p.Cys161Trp (c.483C>G)?

AlphaMissense predicts likely pathogenic (score 0.9003) — an in-silico prediction, not a clinical call.

STRC p.Cys161Trp

c.483C>G · rs769033589 · VCV3171611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9003 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9003	likely pathogenic · top 6% in STRC
REVEL	0.696	pathogenic-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -4, phastCons 0.001
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	17.41	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 0.028% African / African-American · 21/74,940 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00143% 23/1,613,960 alleles · ultra-rare exomes 9/1,461,668 · genomes 14/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,569
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Cys161Trp
Coding: c.483C>G
MANE Select: NM_153700
dbSNP: rs769033589
Type: single nucleotide variant
Location: chr15:43617938 (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-cys161trp (accessed [today's date]).

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