Is CDHR4 p.Leu360Phe (c.1078C>T) pathogenic?

CDHR4 p.Leu360Phe (c.1078C>T) is classified Likely benign in CDHR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). AlphaMissense: likely benign (0.0847); Ultra-rare (popmax 0.088%, sas).

How common is CDHR4 p.Leu360Phe (c.1078C>T) in the general population?

CDHR4 p.Leu360Phe (c.1078C>T) is ultra-rare (popmax 0.088%, sas) (gnomAD).

What do computational predictors say about CDHR4 p.Leu360Phe (c.1078C>T)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

CDHR4 p.Leu360Phe

c.1078C>T · VCV3265381

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.088%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -4.92	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 0.2	GERP -3, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 8,977 bp · p 0.0033 · regional, not allelic
Overall
CADD	0.157	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 0.088% South Asian · 74/84,064 alleles

Filtering AF 0.0718% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.066%

Overall 0.00535% 83/1,551,730 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.088%	1,136
Remaining individualsnot grpmax-eligible	0.0116%	8,588
European (non-Finnish)	0.000174%	573,496

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.Leu360Phe
Coding: c.1078C>T
MANE Select: NM_001007540
Type: single nucleotide variant
Location: chr3:49795054 (GRCh38)
Gene constraint: LOEUF 1.174 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.90
Residue 360: 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-leu360phe (accessed [today's date]).

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