Is CELSR3 p.Asp3302His (c.9904G>C) pathogenic?

CELSR3 p.Asp3302His (c.9904G>C) is classified Benign in CELSR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely pathogenic (0.5951); Common (popmax 6.04%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CELSR3 p.Asp3302His (c.9904G>C)?

AlphaMissense predicts likely pathogenic (score 0.5951) — an in-silico prediction, not a clinical call.

CELSR3 p.Asp3302His

Q: How common is CELSR3 p.Asp3302His (c.9904G>C) in the general population?

CELSR3 p.Asp3302His (c.9904G>C) is common (popmax 6.04%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9904G>C · rs61729240 · VCV783378

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5951 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.04%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
AlphaMissense	0.5951	likely pathogenic
REVEL	0.366	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.0024 · regional, not allelic
Overall
CADD	24.6	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 6.04% African / African-American · 4,527/75,000 alleles

Filtering AF 5.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.83%

Overall 0.329% 5,304/1,613,294 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.04%	17
Middle Eastern	0.611%	164
Remaining individualsnot grpmax-eligible	0.483%	207
Admixed American	0.42%	238
South Asian	0.034%	2,937
European (non-Finnish)	0.0131%	7,612

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: CELSR3
Protein: p.Asp3302His
Coding: c.9904G>C
MANE Select: NM_001407
dbSNP: rs61729240
Type: single nucleotide variant
Location: chr3:48639681 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 3302: the 'disordered' region

Full CELSR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR3 p.Ala2862Val Uncertain significance ★★ ⚠ same type
CELSR3 p.Arg2345His Uncertain significance ★★ ⚠ same type
CELSR3 p.Gly2265Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Val1107Met Uncertain significance ★★ same type
CELSR3 p.Arg2886= Likely benign ★★ same type
CELSR3 p.Arg3189Gln Benign/Likely benign ★★ same type
CELSR3 p.Arg3201Gln Benign ★★ 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/celsr3-p-asp3302his (accessed [today's date]).

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