Is CDHR5 p.Pro48Leu (c.143C>T) pathogenic?

CDHR5 p.Pro48Leu (c.143C>T) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). AlphaMissense: ambiguous (0.3687); Very rare (popmax 0.00891%, eas).

How common is CDHR5 p.Pro48Leu (c.143C>T) in the general population?

CDHR5 p.Pro48Leu (c.143C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CDHR5 p.Pro48Leu (c.143C>T)?

AlphaMissense predicts ambiguous (score 0.3687) — an in-silico prediction, not a clinical call.

CDHR5 p.Pro48Leu

c.143C>T · VCV3265396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3687	ambiguous
REVEL	0.16	moderately benign-leaning
SaProt	LLR -15.10	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	22.1	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 0.00891% East Asian · 4/44,874 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000558% 9/1,613,302 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,218
African / African-American	0.00267%	37,463
Admixed American	0.00167%	59,956
European (non-Finnish)	0.00017%	589,776

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.Pro48Leu
Coding: c.143C>T
MANE Select: NM_021924
Type: single nucleotide variant
Location: chr11:624675 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB

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-pro48leu (accessed [today's date]).

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