Is CDH5 p.Ala628Val (c.1883C>T) pathogenic?

CDH5 p.Ala628Val (c.1883C>T) is classified Uncertain significance in CDH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.1266); Absent from gnomAD v4.1.

How common is CDH5 p.Ala628Val (c.1883C>T) in the general population?

CDH5 p.Ala628Val (c.1883C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH5 p.Ala628Val (c.1883C>T)?

AlphaMissense predicts likely benign (score 0.1266) — an in-silico prediction, not a clinical call.

CDH5 p.Ala628Val

c.1883C>T · VCV3830198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1266 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,058)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1266	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -7.30	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 1.9	GERP -0.097, phastCons 0.94
Regional constraint	o/e 0.88	unconstrained · MANE · 24 kb · p 0.00013 · regional, not allelic
Overall
CADD	19.25	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

No allele count reported in gnomAD v4.1 (AN 1,608,058). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH5
Protein: p.Ala628Val
Coding: c.1883C>T
MANE Select: NM_001795
Type: single nucleotide variant
Location: chr16:66402697 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.46
Residue 628: the 'required for interaction with pals1' region

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-ala628val (accessed [today's date]).

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