Is WHRN p.Pro311= (c.933A>C) pathogenic?

WHRN p.Pro311= (c.933A>C) is classified Conflicting classifications of pathogenicity in WHRN (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-28). Rare (popmax 0.979%, sas); Associated with Usher syndrome type 2D.

What condition is associated with WHRN p.Pro311= (c.933A>C)?

WHRN p.Pro311= (c.933A>C) is associated with Usher syndrome type 2D, autosomal recessive nonsyndromic hearing loss 31 (ClinVar).

How common is WHRN p.Pro311= (c.933A>C) in the general population?

WHRN p.Pro311= (c.933A>C) is rare (popmax 0.979%, sas) (gnomAD).

WHRN p.Pro311=

c.933A>C · rs569159249 · VCV289015

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.979%, sas)

Conditions

Usher syndrome type 2D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -4.1
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.979% South Asian · 892/91,090 alleles

Filtering AF 0.926% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.905%

Overall 0.0591% 954/1,614,116 alleles · rare exomes 902/1,461,786 · genomes 52/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.979%	102
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
African / African-American	0.00266%	37,527
Finnishnot grpmax-eligible	0.00156%	63,950
European (non-Finnish)	0.00153%	65,557

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: WHRN
Protein: p.Pro311=
Coding: c.933A>C
MANE Select: NM_015404
dbSNP: rs569159249
Type: single nucleotide variant
Location: chr9:114466297 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 59.39 · 5 PDB
Residue 311: the pdz 2 domain

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

Also linked: autosomal recessive nonsyndromic hearing loss 31

Similar variants

WHRN p.Pro311Ser Uncertain significance ★ ⚠ same residue
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.Arg490His 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-pro311 (accessed [today's date]).

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