Is CELF3 p.Ala312Val (c.935C>T) pathogenic?

CELF3 p.Ala312Val (c.935C>T) is classified Uncertain significance in CELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0776); Ultra-rare (popmax 0.0452%, afr).

How common is CELF3 p.Ala312Val (c.935C>T) in the general population?

CELF3 p.Ala312Val (c.935C>T) is ultra-rare (popmax 0.0452%, afr) (gnomAD).

What do computational predictors say about CELF3 p.Ala312Val (c.935C>T)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CELF3 p.Ala312Val

c.935C>T · rs372369954 · VCV2400994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0452%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.05	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 12	GERP -2.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,059 bp · p 0.068 · regional, not allelic
Overall
CADD	23.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0452% African / African-American · 33/73,032 alleles

Filtering AF 0.033% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0289%

Overall 0.00361% 56/1,550,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0452%	2,213
Admixed American	0.0059%	16,957
Remaining individualsnot grpmax-eligible	0.005%	20,007
South Asian	0.00357%	27,987
European (non-Finnish)	0.00122%	81,881

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: CELF3
Protein: p.Ala312Val
Coding: c.935C>T
MANE Select: NM_007185
dbSNP: rs372369954
Type: single nucleotide variant
Location: chr1:151706722 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 1 PDB

Full CELF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF3 p.Ala146Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala206Ser Uncertain significance ★ ⚠ same type
CELF3 p.Ala206Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala216Glu Uncertain significance ★ ⚠ same type
CELF3 p.Ala221Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala276Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala323Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala334Pro 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/celf3-p-ala312val (accessed [today's date]).

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