Is CDHR5 p.Gln549Arg (c.1646A>G) pathogenic?

CDHR5 p.Gln549Arg (c.1646A>G) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.0958); Ultra-rare (popmax 0.0376%, nfe).

How common is CDHR5 p.Gln549Arg (c.1646A>G) in the general population?

CDHR5 p.Gln549Arg (c.1646A>G) is ultra-rare (popmax 0.0376%, nfe) (gnomAD).

What do computational predictors say about CDHR5 p.Gln549Arg (c.1646A>G)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

CDHR5 p.Gln549Arg

c.1646A>G · rs151089830 · VCV2344735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0376%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -11.29	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 -5.5	GERP -1.6
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	0.018	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 0.0376% European (non-Finnish) · 443/1,176,706 alleles

Filtering AF 0.0347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.0308% 496/1,607,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0376%	2,656
Remaining individualsnot grpmax-eligible	0.0371%	2,699
Admixed American	0.0268%	3,731
African / African-American	0.0121%	8,248
Ashkenazi Jewishnot grpmax-eligible	0.00681%	14,678
Finnishnot grpmax-eligible	0.00313%	31,922
South Asian	0.0011%	90,912

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.Gln549Arg
Coding: c.1646A>G
MANE Select: NM_021924
dbSNP: rs151089830
Type: single nucleotide variant
Location: chr11:618913 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB
Residue 549: 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-gln549arg (accessed [today's date]).

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