Is CELF2 p.Ala410Thr (c.1228G>A) pathogenic?

CELF2 p.Ala410Thr (c.1228G>A) is classified Uncertain significance in CELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.1522); Ultra-rare (popmax 0.0133%, amr).

How common is CELF2 p.Ala410Thr (c.1228G>A) in the general population?

CELF2 p.Ala410Thr (c.1228G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CELF2 p.Ala410Thr (c.1228G>A)?

AlphaMissense predicts likely benign (score 0.1522) — an in-silico prediction, not a clinical call.

CELF2 p.Ala410Thr

c.1228G>A · VCV3489990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1522 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1522	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -6.84	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 0.50	unconstrained · MANE · 156 kb · p 7.3e-29 · regional, not allelic
Overall
CADD	32.0	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 A397T vs ClinVar A410T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,006 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00273% 44/1,612,620 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
African / African-American	0.00801%	12,482
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.00237%	42,143

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: CELF2
Protein: p.Ala410Thr
Coding: c.1228G>A
MANE Select: NM_001326342
Type: single nucleotide variant
Location: chr10:11321320 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.26 · 7 PDB
Residue 410: the 'necessary for rna-binding, tnnt2 exon 5 and nmda r1 exon 21 inclusion' region

Full CELF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF2 p.Arg506Cys Pathogenic/Likely pathogenic ★★ same type
CELF2 p.Arg513His Likely pathogenic ★★ same type
CELF2 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same type
CELF2 p.Ala135Thr Uncertain significance ★★ ⚠ same type
CELF2 p.Val95Leu Uncertain significance ★★ ⚠ same type
CELF2 p.Arg506His Pathogenic ★ same type
CELF2 p.Arg506Leu Pathogenic ★ same type
CELF2 p.Arg513Cys Likely pathogenic ★ 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/celf2-p-ala410thr (accessed [today's date]).

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