Is CDHR3 p.Arg603His (c.1808G>A) pathogenic?

CDHR3 p.Arg603His (c.1808G>A) is classified Likely benign in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.1109); Rare (popmax 0.116%, sas).

How common is CDHR3 p.Arg603His (c.1808G>A) in the general population?

CDHR3 p.Arg603His (c.1808G>A) is rare (popmax 0.116%, sas) (gnomAD).

What do computational predictors say about CDHR3 p.Arg603His (c.1808G>A)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

CDHR3 p.Arg603His

c.1808G>A · VCV3999133

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -8.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 4.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.92 · regional, not allelic
Overall
CADD	23.1	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 0.116% South Asian · 106/91,026 alleles

Filtering AF 0.0984% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0917%

Overall 0.00855% 138/1,613,442 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.116%	859
Middle Eastern	0.0329%	3,038
East Asian	0.00446%	22,442
Admixed American	0.00334%	29,982
European (non-Finnish)	0.00203%	49,153
Remaining individualsnot grpmax-eligible	0.0016%	62,444
Finnishnot grpmax-eligible	0.00156%	63,982

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: CDHR3
Protein: p.Arg603His
Coding: c.1808G>A
MANE Select: NM_152750
Type: single nucleotide variant
Location: chr7:106020527 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 603: the cadherin 6 domain

Full CDHR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR3 p.Arg603Cys Likely benign ★★ ⚠ same residue
CDHR3 c.1653+3G>A Benign/Likely benign ★★ same type
CDHR3 p.Asp337= Benign ★★ same type
CDHR3 p.Gln399= Benign ★★ same type
CDHR3 p.Ala148Ser Uncertain significance ★ ⚠ same type
CDHR3 p.Ala158Asp Uncertain significance ★ ⚠ same type
CDHR3 p.Ala541Asp Uncertain significance ★ ⚠ same type
CDHR3 p.Ala541Val 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/cdhr3-p-arg603his (accessed [today's date]).

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