Is CDH5 p.Val244Met (c.730G>A) pathogenic?

CDH5 p.Val244Met (c.730G>A) is classified Uncertain significance in CDH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: ambiguous (0.5374); Ultra-rare (popmax 0.0418%, amr).

How common is CDH5 p.Val244Met (c.730G>A) in the general population?

CDH5 p.Val244Met (c.730G>A) is ultra-rare (popmax 0.0418%, amr) (gnomAD).

What do computational predictors say about CDH5 p.Val244Met (c.730G>A)?

AlphaMissense predicts ambiguous (score 0.5374) — an in-silico prediction, not a clinical call.

CDH5 p.Val244Met

c.730G>A · rs763466378 · VCV2374492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5374 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0418%, amr)

Computational evidence

Protein change
AlphaMissense	0.5374	ambiguous
REVEL	0.513	indeterminate
SaProt	LLR -13.50	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 24 kb · p 0.00013 · regional, not allelic
Overall
CADD	29.6	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 0.0418% Admixed American · 25/59,824 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00354% 57/1,612,408 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0418%	2,393
East Asian	0.0246%	4,067
South Asian	0.0055%	18,172
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,552
Remaining individualsnot grpmax-eligible	0.00321%	31,197
Finnishnot grpmax-eligible	0.00156%	64,036
African / African-American	0.00134%	74,882
European (non-Finnish)	0.000933%	107,193

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: CDH5
Protein: p.Val244Met
Coding: c.730G>A
MANE Select: NM_001795
dbSNP: rs763466378
Type: single nucleotide variant
Location: chr16:66389471 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.46
Residue 244: the cadherin 2 domain

Full CDH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH5 p.Val266= Benign ★★ same type
CDH5 p.Ala13Ser Uncertain significance ★ ⚠ same type
CDH5 p.Ala187Val Uncertain significance ★ ⚠ same type
CDH5 p.Ala201Ser Uncertain significance ★ ⚠ same type
CDH5 p.Ala21Thr Uncertain significance ★ ⚠ same type
CDH5 p.Ala229Val Uncertain significance ★ ⚠ same type
CDH5 p.Ala353Val Uncertain significance ★ ⚠ same type
CDH5 p.Ala395Thr 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/cdh5-p-val244met (accessed [today's date]).

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