Is CDHR5 p.Gln77Lys (c.229C>A) pathogenic?

CDHR5 p.Gln77Lys (c.229C>A) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely benign (0.1153); Rare (popmax 0.195%, amr).

How common is CDHR5 p.Gln77Lys (c.229C>A) in the general population?

CDHR5 p.Gln77Lys (c.229C>A) is rare (popmax 0.195%, amr) (gnomAD).

What do computational predictors say about CDHR5 p.Gln77Lys (c.229C>A)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

CDHR5 p.Gln77Lys

c.229C>A · rs181719462 · VCV2342542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.195%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -6.78	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 1.3	GERP -2.8, phastCons 0.98
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	14.51	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 0.195% Admixed American · 117/59,848 alleles

Filtering AF 0.167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.156%

Overall 0.0077% 124/1,609,428 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.195%	512
Remaining individualsnot grpmax-eligible	0.00642%	15,570
African / African-American	0.00267%	37,497
European (non-Finnish)	8.5e-05%	1,176,567

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.Gln77Lys
Coding: c.229C>A
MANE Select: NM_021924
dbSNP: rs181719462
Type: single nucleotide variant
Location: chr11:624589 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB
Residue 77: the cadherin 1 domain; a β-strand

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.Ala347Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala364Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala369Val 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-gln77lys (accessed [today's date]).

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