Is CDHR1 p.Val339Ala (c.1016T>C) pathogenic?

CDHR1 p.Val339Ala (c.1016T>C) is classified Uncertain significance in CDHR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-01). AlphaMissense: ambiguous (0.412); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDHR1 p.Val339Ala (c.1016T>C)?

CDHR1 p.Val339Ala (c.1016T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDHR1 p.Val339Ala (c.1016T>C) in the general population?

CDHR1 p.Val339Ala (c.1016T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CDHR1 p.Val339Ala (c.1016T>C)?

AlphaMissense predicts ambiguous (score 0.412) — an in-silico prediction, not a clinical call.

CDHR1 p.Val339Ala

c.1016T>C · rs2492519565 · VCV2007457

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.412	ambiguous
REVEL	0.322	indeterminate
SaProt	LLR -7.10	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 4.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	25.6	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 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very 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: CDHR1
Protein: p.Val339Ala
Coding: c.1016T>C
MANE Select: NM_033100
dbSNP: rs2492519565
Type: single nucleotide variant
Location: chr10:84208226 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 339: the cadherin 3 domain

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDHR1 p.Ala106Thr Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala10Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala118Asp Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala132Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala292Asp Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala393Gly Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala493Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala793Thr 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/cdhr1-p-val339ala (accessed [today's date]).

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