Is CELSR2 p.Val1498= (c.4494C>T) pathogenic?

CELSR2 p.Val1498= (c.4494C>T) is classified Likely benign in CELSR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-11). Rare (popmax 0.125%, afr).

How common is CELSR2 p.Val1498= (c.4494C>T) in the general population?

CELSR2 p.Val1498= (c.4494C>T) is rare (popmax 0.125%, afr) (gnomAD).

CELSR2 p.Val1498=

c.4494C>T · rs139675369 · VCV751076

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.125%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -2.7, phastCons 0.35
Overall
CADD	4.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.125% African / African-American · 94/74,922 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0972%

Overall 0.00607% 98/1,614,038 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.125%	797
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00167%	60,002

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.Val1498=
Coding: c.4494C>T
MANE Select: NM_001408
dbSNP: rs139675369
Type: single nucleotide variant
Location: chr1:109262394 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 1498: the laminin g-like 1 domain

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

Similar variants

CELSR2 p.Val1498Ile Uncertain significance ★ ⚠ same residue
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

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-val1498 (accessed [today's date]).

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