Is CELSR3 p.Gly128Val (c.383G>T) pathogenic?

CELSR3 p.Gly128Val (c.383G>T) is classified Benign in CELSR3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-04-10). AlphaMissense: likely benign (0.0993); Low-frequency (popmax 2.75%, afr).

How common is CELSR3 p.Gly128Val (c.383G>T) in the general population?

CELSR3 p.Gly128Val (c.383G>T) is low-frequency (popmax 2.75%, afr) (gnomAD).

What do computational predictors say about CELSR3 p.Gly128Val (c.383G>T)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

CELSR3 p.Gly128Val

c.383G>T · rs114401810 · VCV767908

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.75%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.105	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Pangolin	Δ0.21	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.5	GERP -3.5, phastCons 0.035
Regional constraint	o/e 1.00	unconstrained · MANE · 1,011 bp · p 0.99 · regional, not allelic
Overall
CADD	18.08	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 2.75% African / African-American · 2,067/75,058 alleles

Filtering AF 2.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.61%

Overall 0.145% 2,337/1,613,156 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.75%	36
Admixed American	0.202%	496
Remaining individualsnot grpmax-eligible	0.168%	595
Middle Eastern	0.165%	606
European (non-Finnish)	0.00271%	36,876
South Asian	0.0022%	45,545

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.Gly128Val
Coding: c.383G>T
MANE Select: NM_001407
dbSNP: rs114401810
Type: single nucleotide variant
Location: chr3:48662252 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)

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

Similar variants

CELSR3 p.Gly128Arg Uncertain significance ★ ⚠ same residue
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

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-gly128val (accessed [today's date]).

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