Is CELSR2 p.Arg91Lys (c.272G>A) pathogenic?

CELSR2 p.Arg91Lys (c.272G>A) is classified Benign in CELSR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.1351); Low-frequency (popmax 3.13%, afr).

How common is CELSR2 p.Arg91Lys (c.272G>A) in the general population?

CELSR2 p.Arg91Lys (c.272G>A) is low-frequency (popmax 3.13%, afr) (gnomAD).

What do computational predictors say about CELSR2 p.Arg91Lys (c.272G>A)?

AlphaMissense predicts likely benign (score 0.1351) — an in-silico prediction, not a clinical call.

CELSR2 p.Arg91Lys

c.272G>A · rs112983744 · VCV791805

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1351 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.13%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1351	likely benign
REVEL	0.209	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 8.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,783 bp · p 0.0042 · regional, not allelic
Overall
CADD	19.05	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 3.13% African / African-American · 2,347/75,054 alleles

Filtering AF 3.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.98%

Overall 0.162% 2,614/1,613,482 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.13%	32
Remaining individualsnot grpmax-eligible	0.192%	521
Admixed American	0.177%	566
Middle Eastern	0.033%	3,031
East Asian	0.0111%	8,974
South Asian	0.00768%	13,013
European (non-Finnish)	0.00229%	43,705

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.Arg91Lys
Coding: c.272G>A
MANE Select: NM_001408
dbSNP: rs112983744
Type: single nucleotide variant
Location: chr1:109250351 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)

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

Similar variants

CELSR2 c.8338+1G>C Uncertain significance ★★ same type
CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1400His Uncertain significance ★★ same type
CELSR2 p.Arg1978Gln 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/celsr2-p-arg91lys (accessed [today's date]).

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