Is USH1C p.Arg792Trp (c.2374C>T) pathogenic?

USH1C p.Arg792Trp (c.2374C>T) is classified Uncertain significance in USH1C (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-07-28). AlphaMissense: likely benign (0.1393); Ultra-rare (popmax 0.0433%, amr); Associated with Inborn genetic diseases.

What condition is associated with USH1C p.Arg792Trp (c.2374C>T)?

USH1C p.Arg792Trp (c.2374C>T) is associated with Inborn genetic diseases, Usher syndrome type 1, Usher syndrome type 1C (ClinVar).

How common is USH1C p.Arg792Trp (c.2374C>T) in the general population?

USH1C p.Arg792Trp (c.2374C>T) is ultra-rare (popmax 0.0433%, amr) (gnomAD).

What do computational predictors say about USH1C p.Arg792Trp (c.2374C>T)?

AlphaMissense predicts likely benign (score 0.1393) — an in-silico prediction, not a clinical call.

USH1C p.Arg792Trp

c.2374C>T · rs200428926 · VCV992072

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1393 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1393	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -12.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.036, phastCons 0.18
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.94 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R492W vs ClinVar R792W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0433% Admixed American · 26/59,990 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00403% 65/1,613,346 alleles · ultra-rare exomes 59/1,461,042 · genomes 6/152,304 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0433%	2,307
South Asian	0.0231%	4,333
Remaining individualsnot grpmax-eligible	0.0048%	20,825
East Asian	0.00223%	44,850
European (non-Finnish)	0.00119%	84,263

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: USH1C
Protein: p.Arg792Trp
Coding: c.2374C>T
MANE Select: NM_153676
dbSNP: rs200428926
Type: single nucleotide variant
Location: chr11:17501057 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 11 PDB
Residue 492 UniProt numbering: the pdz 3 domain; the 'mediates interaction with myo7b' region; an α-helix

Full USH1C 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

Also linked: Usher syndrome type 1 Usher syndrome type 1C autosomal recessive nonsyndromic hearing loss 18A

Similar variants

USH1C p.Arg792= Likely benign ★★ same residue
USH1C p.Arg792Gln Uncertain significance ★★ ⚠ same residue
USH1C p.Arg792Pro Uncertain significance ★ ⚠ same residue
USH1C c.1020-2A>C Likely pathogenic ★★ same condition
USH1C c.104+1G>A Pathogenic/Likely pathogenic ★★ same condition
USH1C c.104+5G>C Likely pathogenic ★★ same condition
USH1C c.105-2A>G Pathogenic/Likely pathogenic ★★ same condition
USH1C c.2185-1G>A 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/ush1c-p-arg792trp (accessed [today's date]).

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