Is WHRN p.Arg55Pro (c.164G>C) pathogenic?

WHRN p.Arg55Pro (c.164G>C) is classified Uncertain significance in WHRN (ClinVar, Single submitter, 2 submitters; last evaluated 2022-09-19). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1; Associated with Usher syndrome type 2D.

What condition is associated with WHRN p.Arg55Pro (c.164G>C)?

WHRN p.Arg55Pro (c.164G>C) is associated with Usher syndrome type 2D (ClinVar).

How common is WHRN p.Arg55Pro (c.164G>C) in the general population?

WHRN p.Arg55Pro (c.164G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WHRN p.Arg55Pro (c.164G>C)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

WHRN p.Arg55Pro

c.164G>C · rs775066754 · VCV829829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 2D

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic · top 1% in WHRN
REVEL	0.469	indeterminate
SaProt	LLR -15.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 102 kb · p 0.96 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WHRN
Protein: p.Arg55Pro
Coding: c.164G>C
MANE Select: NM_015404
dbSNP: rs775066754
Type: single nucleotide variant
Location: chr9:114504638 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 59.39 · 5 PDB

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

Disease context

Usher syndrome type 2D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WHRN c.1417-1G>A Pathogenic/Likely pathogenic ★★ same condition
WHRN p.Arg778Ter Pathogenic ★★ same condition
WHRN c.*156G>A Uncertain significance ★★ same condition
WHRN p.Ala631Val Uncertain significance ★★ ⚠ same condition
WHRN p.Ala885Thr Uncertain significance ★★ ⚠ same condition
WHRN p.Arg366His Uncertain significance ★★ ⚠ same condition
WHRN p.Arg745His Uncertain significance ★★ ⚠ same condition
WHRN p.Arg795Trp Uncertain significance ★★ ⚠ 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/whrn-p-arg55pro (accessed [today's date]).

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