Is CDHR3 p.Val732Ile (c.2194G>A) pathogenic?

CDHR3 p.Val732Ile (c.2194G>A) is classified Likely benign in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-09). AlphaMissense: likely benign (0.0656); Rare (popmax 0.741%, afr).

How common is CDHR3 p.Val732Ile (c.2194G>A) in the general population?

CDHR3 p.Val732Ile (c.2194G>A) is rare (popmax 0.741%, afr) (gnomAD).

What do computational predictors say about CDHR3 p.Val732Ile (c.2194G>A)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

CDHR3 p.Val732Ile

c.2194G>A · rs11505886 · VCV778939

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.741%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -6.43	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 -5.7	GERP -10
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.92 · regional, not allelic
Overall
CADD	0.017	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 0.741% African / African-American · 556/75,024 alleles

Filtering AF 0.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.67%

Overall 0.0413% 666/1,613,968 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.741%	135
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Admixed American	0.0383%	2,609
Middle Eastern	0.0165%	6,062
South Asian	0.00659%	15,179
European (non-Finnish)	0.00415%	24,079
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,884

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: CDHR3
Protein: p.Val732Ile
Coding: c.2194G>A
MANE Select: NM_152750
dbSNP: rs11505886
Type: single nucleotide variant
Location: chr7:106024498 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB

Full CDHR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR3 c.1653+3G>A Benign/Likely benign ★★ same type
CDHR3 p.Arg603Cys Likely benign ★★ ⚠ same type
CDHR3 p.Asp337= Benign ★★ same type
CDHR3 p.Gln399= Benign ★★ same type
CDHR3 p.Ala148Ser Uncertain significance ★ ⚠ same type
CDHR3 p.Ala158Asp Uncertain significance ★ ⚠ same type
CDHR3 p.Ala541Asp Uncertain significance ★ ⚠ same type
CDHR3 p.Ala541Val 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/cdhr3-p-val732ile (accessed [today's date]).

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