Is CELSR3 p.Ser1738Leu (c.5213C>T) pathogenic?

CELSR3 p.Ser1738Leu (c.5213C>T) is classified Likely benign in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely benign (0.0827); Ultra-rare (popmax 0.033%, mid).

How common is CELSR3 p.Ser1738Leu (c.5213C>T) in the general population?

CELSR3 p.Ser1738Leu (c.5213C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CELSR3 p.Ser1738Leu (c.5213C>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

CELSR3 p.Ser1738Leu

c.5213C>T · rs199541002 · VCV2353955

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.056	moderately 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 1.2	GERP -4.9, phastCons 0.61
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	14.31	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0161% 259/1,613,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.02%	5,004
European (non-Finnish)	0.0188%	5,315
Remaining individualsnot grpmax-eligible	0.0176%	5,682
South Asian	0.00549%	18,217
Finnishnot grpmax-eligible	0.00474%	21,091
Admixed American	0.00167%	60,034

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.Ser1738Leu
Coding: c.5213C>T
MANE Select: NM_001407
dbSNP: rs199541002
Type: single nucleotide variant
Location: chr3:48653943 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 1738: the egf-like 4; calcium-binding domain; a disulfide bond

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-ser1738leu (accessed [today's date]).

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