Is CELSR2 p.Arg2191His (c.6572G>A) pathogenic?

CELSR2 p.Arg2191His (c.6572G>A) is classified Likely benign in CELSR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.2067); Low-frequency (popmax 1.06%, eas); Associated with CELSR2-related disorder.

What condition is associated with CELSR2 p.Arg2191His (c.6572G>A)?

CELSR2 p.Arg2191His (c.6572G>A) is associated with CELSR2-related disorder (ClinVar).

How common is CELSR2 p.Arg2191His (c.6572G>A) in the general population?

CELSR2 p.Arg2191His (c.6572G>A) is low-frequency (popmax 1.06%, eas) (gnomAD).

What do computational predictors say about CELSR2 p.Arg2191His (c.6572G>A)?

AlphaMissense predicts likely benign (score 0.2067) — an in-silico prediction, not a clinical call.

CELSR2 p.Arg2191His

c.6572G>A · rs79850681 · VCV3054241

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2067 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

CELSR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.2067	likely benign
REVEL	0.213	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	24.3	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 1.06% East Asian · 476/44,860 alleles

Filtering AF 0.982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.951%

Overall 0.04% 646/1,613,682 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.06%	94
Middle Eastern	0.0495%	2,021
Admixed American	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0256%	3,906
South Asian	0.0121%	8,279
European (non-Finnish)	0.00983%	10,170
African / African-American	0.00799%	12,510

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: CELSR2
Protein: p.Arg2191His
Coding: c.6572G>A
MANE Select: NM_001408
dbSNP: rs79850681
Type: single nucleotide variant
Location: chr1:109268949 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)

Full CELSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELSR2-related disorder

Similar variants

CELSR2 p.Arg426Ter Uncertain significance same condition
CELSR2 p.Arg881Ter Uncertain significance same condition
CELSR2 p.Ala2579= Likely benign same condition
CELSR2 p.Arg2015= Benign same condition
CELSR2 p.Asn1182= Likely benign same condition
CELSR2 p.Asn1830= Likely benign same condition
CELSR2 p.Gln2053= Likely benign same condition
CELSR2 p.Ile2250= Likely benign same condition

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/celsr2-p-arg2191his (accessed [today's date]).

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