Is CELF1 p.Met280Val (c.838A>G) pathogenic?

CELF1 p.Met280Val (c.838A>G) is classified Uncertain significance in CELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0585); Ultra-rare (popmax 0.0155%, sas).

How common is CELF1 p.Met280Val (c.838A>G) in the general population?

CELF1 p.Met280Val (c.838A>G) is ultra-rare (popmax 0.0155%, sas) (gnomAD).

What do computational predictors say about CELF1 p.Met280Val (c.838A>G)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

CELF1 p.Met280Val

c.838A>G · VCV4225184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 27 kb · p 1.2e-24 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M253V vs ClinVar M280V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0155% South Asian · 14/90,568 alleles

Filtering AF 0.00934% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00739%

Overall 0.00112% 18/1,611,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0155%	6,469
East Asian	0.00223%	44,840
European (non-Finnish)	0.000254%	392,974

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: CELF1
Protein: p.Met280Val
Coding: c.838A>G
MANE Select: NM_001376376
Type: single nucleotide variant
Location: chr11:47478883 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 8 PDB
Residue 280: the 'disordered' region

Full CELF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF1 p.Ser507= Benign ★★ same type
CELF1 c.606+2T>A Uncertain significance ★ same type
CELF1 p.Ala237Thr Uncertain significance ★ ⚠ same type
CELF1 p.Ala401Val Uncertain significance ★ ⚠ same type
CELF1 p.Ala99Val Uncertain significance ★ ⚠ same type
CELF1 p.Arg152Gln Uncertain significance ★ ⚠ same type
CELF1 p.Arg506His Uncertain significance ★ ⚠ same type
CELF1 p.Arg60Gln 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/celf1-p-met280val (accessed [today's date]).

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