Is CLDN14 p.Val85Asp (c.254T>A) pathogenic?

CLDN14 p.Val85Asp (c.254T>A) is classified Pathogenic in CLDN14 (ClinVar, Single submitter, 4 submitters; last evaluated 2022-05-22). AlphaMissense: likely pathogenic (0.9377); Ultra-rare (popmax 0.0176%, sas); Associated with autosomal recessive nonsyndromic hearing loss 29.

What condition is associated with CLDN14 p.Val85Asp (c.254T>A)?

CLDN14 p.Val85Asp (c.254T>A) is associated with autosomal recessive nonsyndromic hearing loss 29, hearing loss disorder, hearing loss, autosomal recessive (ClinVar).

How common is CLDN14 p.Val85Asp (c.254T>A) in the general population?

CLDN14 p.Val85Asp (c.254T>A) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about CLDN14 p.Val85Asp (c.254T>A)?

AlphaMissense predicts likely pathogenic (score 0.9377) — an in-silico prediction, not a clinical call.

CLDN14 p.Val85Asp

c.254T>A · rs74315437 · VCV4851

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9377 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 29

Computational evidence

Protein change
AlphaMissense	0.9377	likely pathogenic ✓ concordant with ClinVar
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -14.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 716 bp · p 0.098 · regional, not allelic
Overall
CADD	28.1	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 0.0176% South Asian · 16/91,082 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000992% 16/1,613,198 alleles · ultra-rare

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: CLDN14
Protein: p.Val85Asp
Coding: c.254T>A
dbSNP: rs74315437
Type: single nucleotide variant
Location: chr21:36461442 (GRCh38)

Full CLDN14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hearing loss disorder hearing loss, autosomal recessive

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/cldn14-p-val85asp (accessed [today's date]).

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