Is CDHR5 p.Ala347Val (c.1040C>T) pathogenic?

CDHR5 p.Ala347Val (c.1040C>T) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.1436); Ultra-rare (popmax 0.0255%, eas).

How common is CDHR5 p.Ala347Val (c.1040C>T) in the general population?

CDHR5 p.Ala347Val (c.1040C>T) is ultra-rare (popmax 0.0255%, eas) (gnomAD).

What do computational predictors say about CDHR5 p.Ala347Val (c.1040C>T)?

AlphaMissense predicts likely benign (score 0.1436) — an in-silico prediction, not a clinical call.

CDHR5 p.Ala347Val

c.1040C>T · rs760880719 · VCV2388197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1436 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0255%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1436	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -1.2
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	11.14	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0255% East Asian · 11/43,162 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.00342% 54/1,577,240 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0255%	3,924
South Asian	0.0183%	5,467
Middle Eastern	0.0166%	6,018
Remaining individualsnot grpmax-eligible	0.00327%	30,621
European (non-Finnish)	0.00197%	50,680
African / African-American	0.00135%	74,290

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: CDHR5
Protein: p.Ala347Val
Coding: c.1040C>T
MANE Select: NM_021924
dbSNP: rs760880719
Type: single nucleotide variant
Location: chr11:619820 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB
Residue 347: the cadherin 3 domain

Full CDHR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR5 p.Arg182His Benign ★★ same type
CDHR5 p.Gly298= Benign ★★ same type
CDHR5 p.Ala151Pro Uncertain significance ★ ⚠ same type
CDHR5 p.Ala171Thr Uncertain significance ★ ⚠ same type
CDHR5 p.Ala230Thr Uncertain significance ★ ⚠ same type
CDHR5 p.Ala364Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala369Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala398Thr Uncertain significance ★ ⚠ same type

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/cdhr5-p-ala347val (accessed [today's date]).

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