Is CDHR4 p.Arg379His (c.1136G>A) pathogenic?

CDHR4 p.Arg379His (c.1136G>A) is classified Likely benign in CDHR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0548); Ultra-rare (popmax 0.0166%, mid).

How common is CDHR4 p.Arg379His (c.1136G>A) in the general population?

CDHR4 p.Arg379His (c.1136G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CDHR4 p.Arg379His (c.1136G>A)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

CDHR4 p.Arg379His

c.1136G>A · rs767933275 · VCV2214301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.25	GERP -0.55, phastCons 0.063
Regional constraint	o/e 0.91	unconstrained · MANE · 8,977 bp · p 0.0033 · regional, not allelic
Overall
CADD	1.376	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 0.0166% Middle Eastern · 1/6,014 alleles

Filtering AF 0.00641% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00595%

Overall 0.00606% 94/1,551,530 alleles · ultra-rare exomes 93/1,399,378 · genomes 1/152,152 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,014
European (non-Finnish)	0.00776%	12,888
South Asian	0.00238%	42,031
Admixed American	0.00196%	50,982
Remaining individualsnot grpmax-eligible	0.00166%	60,088

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: CDHR4
Protein: p.Arg379His
Coding: c.1136G>A
MANE Select: NM_001007540
dbSNP: rs767933275
Type: single nucleotide variant
Location: chr3:49794996 (GRCh38)
Gene constraint: LOEUF 1.174 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.90
Residue 379: the cadherin 2 domain

Full CDHR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR4 p.Ala12Val Uncertain significance ★ ⚠ same type
CDHR4 p.Ala149Val Uncertain significance ★ ⚠ same type
CDHR4 p.Ala302Val Uncertain significance ★ ⚠ same type
CDHR4 p.Ala310Pro Uncertain significance ★ ⚠ same type
CDHR4 p.Ala318Asp Uncertain significance ★ ⚠ same type
CDHR4 p.Ala341Pro Uncertain significance ★ ⚠ same type
CDHR4 p.Ala385Gly Uncertain significance ★ ⚠ same type
CDHR4 p.Ala456Pro 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/cdhr4-p-arg379his (accessed [today's date]).

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