Is STRC p.Arg92Trp (c.274C>T) pathogenic?

STRC p.Arg92Trp (c.274C>T) is classified Uncertain significance in STRC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-06-07). AlphaMissense: likely benign (0.2192); Ultra-rare (popmax 0.028%, mid); Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Arg92Trp (c.274C>T)?

STRC p.Arg92Trp (c.274C>T) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

How common is STRC p.Arg92Trp (c.274C>T) in the general population?

STRC p.Arg92Trp (c.274C>T) is ultra-rare (popmax 0.028%, mid) (gnomAD).

What do computational predictors say about STRC p.Arg92Trp (c.274C>T)?

AlphaMissense predicts likely benign (score 0.2192) — an in-silico prediction, not a clinical call.

STRC p.Arg92Trp

c.274C>T · rs1484849703 · VCV440309

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2192 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 16

Computational evidence

Protein change
AlphaMissense	0.2192	likely benign
REVEL	0.585	indeterminate
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.028% Middle Eastern · 1/3,566 alleles

Filtering AF 0.0164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.00662% 73/1,103,102 alleles · ultra-rare exomes 63/966,556 · genomes 10/136,546 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.028%	3,566
African / African-American	0.0268%	3,731
Remaining individualsnot grpmax-eligible	0.0132%	7,595
South Asian	0.0122%	8,188
European (non-Finnish)	0.00526%	19,028
East Asian	0.00262%	38,122
Admixed American	0.00204%	49,008

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.Arg92Trp
Coding: c.274C>T
MANE Select: NM_153700
dbSNP: rs1484849703
Type: single nucleotide variant
Location: chr15:43618147 (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

autosomal recessive nonsyndromic hearing loss 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC p.Arg92Gln Uncertain significance ★★ ⚠ same residue
STRC p.Arg92Pro Uncertain significance ★ same residue
STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1073Ter Pathogenic ★★ same condition
STRC p.Arg1154Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1224Ter Pathogenic ★★ same condition
STRC p.Arg1338Ter 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-arg92trp (accessed [today's date]).

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