Is CLDN14 p.Val6= (c.18G>A) pathogenic?

CLDN14 p.Val6= (c.18G>A) is classified Conflicting classifications of pathogenicity in CLDN14 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-02-24). Very rare (popmax 0.00195%, amr); Associated with autosomal recessive nonsyndromic hearing loss 29.

What condition is associated with CLDN14 p.Val6= (c.18G>A)?

CLDN14 p.Val6= (c.18G>A) is associated with autosomal recessive nonsyndromic hearing loss 29 (ClinVar).

How common is CLDN14 p.Val6= (c.18G>A) in the general population?

CLDN14 p.Val6= (c.18G>A) is very rare (popmax 0.00195%, amr) (gnomAD).

CLDN14 p.Val6=

c.18G>A · rs387907417 · VCV64487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00195%, amr)

Conditions

autosomal recessive nonsyndromic hearing loss 29

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.29	GERP -3.9, phastCons 0.98
Overall
CADD	4.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% Admixed American · 1/51,310 alleles

Filtering AF 0.000784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000621%

Overall 0.00103% 16/1,553,328 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00195%	51,310
European (non-Finnish)	0.00131%	76,606

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.Val6=
Coding: c.18G>A
dbSNP: rs387907417
Type: single nucleotide variant
Location: chr21:36461678 (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

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-val6 (accessed [today's date]).

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