Is CDHR5 p.Pro597Leu (c.1790C>T) pathogenic?

CDHR5 p.Pro597Leu (c.1790C>T) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1259); Ultra-rare (popmax 0.058%, amr).

How common is CDHR5 p.Pro597Leu (c.1790C>T) in the general population?

CDHR5 p.Pro597Leu (c.1790C>T) is ultra-rare (popmax 0.058%, amr) (gnomAD).

What do computational predictors say about CDHR5 p.Pro597Leu (c.1790C>T)?

AlphaMissense predicts likely benign (score 0.1259) — an in-silico prediction, not a clinical call.

CDHR5 p.Pro597Leu

c.1790C>T · rs761307013 · VCV2596252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1259 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.058%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1259	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -10.69	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.56, phastCons 0.004
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	18.74	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 0.058% Admixed American · 34/58,618 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0373%

Overall 0.00224% 36/1,605,584 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.058%	1,724
Remaining individualsnot grpmax-eligible	0.00322%	31,028

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.Pro597Leu
Coding: c.1790C>T
MANE Select: NM_021924
dbSNP: rs761307013
Type: single nucleotide variant
Location: chr11:618769 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB
Residue 597: the 'disordered' region; the '4 x 31 aa approximate tandem repeats' region

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-pro597leu (accessed [today's date]).

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