Is CDH19 p.Thr271Ser (c.811A>T) pathogenic?

CDH19 p.Thr271Ser (c.811A>T) is classified Uncertain significance in CDH19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely benign (0.093); Very rare (popmax 0.00908%, nfe).

How common is CDH19 p.Thr271Ser (c.811A>T) in the general population?

CDH19 p.Thr271Ser (c.811A>T) is very rare (popmax 0.00908%, nfe) (gnomAD).

What do computational predictors say about CDH19 p.Thr271Ser (c.811A>T)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

CDH19 p.Thr271Ser

c.811A>T · VCV3265211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00908%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.06	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 -2.5	GERP -5.8
Regional constraint	o/e 1.11	unconstrained · MANE · 67 kb · p 0.00092 · regional, not allelic
Overall
CADD	4.959	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 0.00908% European (non-Finnish) · 107/1,179,054 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00709%

Overall 0.00664% 107/1,611,698 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: CDH19
Protein: p.Thr271Ser
Coding: c.811A>T
MANE Select: NM_021153
Type: single nucleotide variant
Location: chr18:66544868 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.14
Residue 271: the cadherin 3 domain

Full CDH19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH19 p.Pro558= Benign ★★ same type
CDH19 p.Thr89Ile Benign ★★ same type
CDH7 c.1612+22C>T Benign ★★ same type
CDH7 c.1612+24A>T Benign ★★ same type
CDH7 c.1612+81T>C Benign ★★ same type
CDH7 c.1864+225A>G Benign ★★ same type
CDH7 c.210+52G>A Benign ★★ same type
CDH7 c.210+56T>G Benign ★★ 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/cdh19-p-thr271ser (accessed [today's date]).

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