Is USH1C p.Arg155Pro (c.464G>C) pathogenic?

USH1C p.Arg155Pro (c.464G>C) is classified Uncertain significance in USH1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-06). AlphaMissense: likely pathogenic (0.9821); Rare (popmax 0.629%, eas); Associated with Usher syndrome type 1C.

What condition is associated with USH1C p.Arg155Pro (c.464G>C)?

USH1C p.Arg155Pro (c.464G>C) is associated with Usher syndrome type 1C (ClinVar).

How common is USH1C p.Arg155Pro (c.464G>C) in the general population?

USH1C p.Arg155Pro (c.464G>C) is rare (popmax 0.629%, eas) (gnomAD).

What do computational predictors say about USH1C p.Arg155Pro (c.464G>C)?

AlphaMissense predicts likely pathogenic (score 0.9821) — an in-silico prediction, not a clinical call.

USH1C p.Arg155Pro

c.464G>C · rs142730611 · VCV303814

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9821 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.629%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1C

Computational evidence

Protein change
AlphaMissense	0.9821	likely pathogenic · top 5% in USH1C
REVEL	0.263	benign-leaning
SaProt	LLR -12.63	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 2.2	GERP 1.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.94 · regional, not allelic
Overall
CADD	26.9	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 0.629% East Asian · 280/44,514 alleles

Filtering AF 0.568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.545%

Overall 0.0177% 284/1,608,568 alleles · rare exomes 276/1,460,054 · genomes 8/148,514 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.629%	159
Remaining individualsnot grpmax-eligible	0.00641%	15,593

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.Arg155Pro
Coding: c.464G>C
MANE Select: NM_153676
dbSNP: rs142730611
Type: single nucleotide variant
Location: chr11:17527255 (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 155: the pdz 1 domain

Full USH1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH1C p.Arg155Ter Pathogenic ★★ same residue
USH1C p.Arg155Gln 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.2227-1G>T Pathogenic/Likely pathogenic ★★ same condition
USH1C c.2280+2T>C Likely pathogenic ★★ same condition
USH1C c.248+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-arg155pro (accessed [today's date]).

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