Is USH1C p.Pro396Arg (c.1187C>G) pathogenic?

USH1C p.Pro396Arg (c.1187C>G) is classified Uncertain significance in USH1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely benign (0.0897); No allele count reported in gnomAD v4.1 (AN 1,614,076).

How common is USH1C p.Pro396Arg (c.1187C>G) in the general population?

USH1C p.Pro396Arg (c.1187C>G) is no allele count reported in gnomAD v4.1 (AN 1,614,076) (gnomAD).

What do computational predictors say about USH1C p.Pro396Arg (c.1187C>G)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

USH1C p.Pro396Arg

c.1187C>G · rs781424965 · VCV2114021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,076)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.94 · regional, not allelic
Overall
CADD	23.1	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

No allele count reported in gnomAD v4.1 (AN 1,614,076). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: USH1C
Protein: p.Pro396Arg
Coding: c.1187C>G
MANE Select: NM_153676
dbSNP: rs781424965
Type: single nucleotide variant
Location: chr11:17520893 (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 396: the 'mediates interaction with myo7b' region

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

Similar variants

USH1C p.Pro396= Benign ★★ same residue
USH1C p.Pro396Ala Uncertain significance ★ ⚠ same residue
USH1C p.Pro396Leu Uncertain significance ★★ 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-pro396arg (accessed [today's date]).

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