Is CDH5 p.Asp57Val (c.170A>T) pathogenic?

CDH5 p.Asp57Val (c.170A>T) is classified Uncertain significance in CDH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: ambiguous (0.4171); Very rare (popmax 0.00492%, nfe).

How common is CDH5 p.Asp57Val (c.170A>T) in the general population?

CDH5 p.Asp57Val (c.170A>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about CDH5 p.Asp57Val (c.170A>T)?

AlphaMissense predicts ambiguous (score 0.4171) — an in-silico prediction, not a clinical call.

CDH5 p.Asp57Val

c.170A>T · VCV3488993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4171	ambiguous
REVEL	0.19	benign-leaning
SaProt	LLR -7.40	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 24 kb · p 0.00013 · regional, not allelic
Overall
CADD	18.59	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 0.00492% European (non-Finnish) · 58/1,180,044 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00378% 61/1,614,116 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,346
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0011%	91,084

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.Asp57Val
Coding: c.170A>T
MANE Select: NM_001795
Type: single nucleotide variant
Location: chr16:66379507 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.46
Residue 57: the cadherin 1 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-asp57val (accessed [today's date]).

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