Is USH1C p.Arg792Pro (c.2375G>C) pathogenic?

USH1C p.Arg792Pro (c.2375G>C) is classified Uncertain significance in USH1C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). AlphaMissense: likely pathogenic (0.7249); Very rare (popmax 0.00223%, eas).

How common is USH1C p.Arg792Pro (c.2375G>C) in the general population?

USH1C p.Arg792Pro (c.2375G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about USH1C p.Arg792Pro (c.2375G>C)?

AlphaMissense predicts likely pathogenic (score 0.7249) — an in-silico prediction, not a clinical call.

USH1C p.Arg792Pro

c.2375G>C · rs563952065 · VCV952789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7249	likely pathogenic
REVEL	0.197	benign-leaning
SaProt	LLR -15.21	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 2.1, phastCons 0.004
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.94 · regional, not allelic
Overall
CADD	21.5	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 R492P vs ClinVar R792P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,830 alleles

Overall 0.000124% 2/1,613,422 alleles · very rare exomes 2/1,461,078 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,830
European (non-Finnish)	8.48e-05%	1,179,734

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.Arg792Pro
Coding: c.2375G>C
MANE Select: NM_153676
dbSNP: rs563952065
Type: single nucleotide variant
Location: chr11:17501056 (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

Similar variants

USH1C p.Arg792Gln Uncertain significance ★★ ⚠ same residue
USH1C p.Arg792Trp Uncertain significance ★★ ⚠ same residue
USH1C p.Arg792= Likely benign ★★ same residue
USH1C c.1020-2A>C Likely pathogenic ★★ same type
USH1C c.104+1G>A Pathogenic/Likely pathogenic ★★ same type
USH1C c.104+5G>C Likely pathogenic ★★ same type
USH1C c.105-2A>G Pathogenic/Likely pathogenic ★★ same type
USH1C c.2185-1G>A Likely pathogenic ★★ same type

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-arg792pro (accessed [today's date]).

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