Is WHRN p.Val39= (c.117G>A) pathogenic?

WHRN p.Val39= (c.117G>A) is classified Benign in WHRN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 37%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 31.

What condition is associated with WHRN p.Val39= (c.117G>A)?

WHRN p.Val39= (c.117G>A) is associated with autosomal recessive nonsyndromic hearing loss 31, Usher syndrome type 2D (ClinVar).

WHRN p.Val39=

Q: How common is WHRN p.Val39= (c.117G>A) in the general population?

WHRN p.Val39= (c.117G>A) is common (popmax 37%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.117G>A · rs2297815 · VCV45644

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 37%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

autosomal recessive nonsyndromic hearing loss 31

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 4.8	GERP 1.8, phastCons 1
Overall
CADD	14.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 37% European (non-Finnish) · 434,574/1,173,868 alleles

Filtering AF 36.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.9%

Overall 35% 558,020/1,592,880 alleles · common exomes 508,433/1,440,726 · genomes 49,587/152,154 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	49.1%	2
European (non-Finnish)grpmax	37%	3
Ashkenazi Jewishnot grpmax-eligible	35.2%	3
Amishnot grpmax-eligible	33.8%	3
Admixed American	32.9%	3
Remaining individualsnot grpmax-eligible	32.5%	3
Middle Eastern	30.4%	3
African / African-American	23.2%	4
South Asian	22.6%	4
East Asian	16.8%	6

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val39=
Coding: c.117G>A
MANE Select: NM_015404
dbSNP: rs2297815
Type: single nucleotide variant
Location: chr9:114504685 (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

autosomal recessive nonsyndromic hearing loss 31 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 2D

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.Arg490His Uncertain significance ★★ ⚠ same condition
WHRN p.Arg745His 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-val39 (accessed [today's date]).

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