Is CELF2 p.Lys508Thr (c.1523A>C) pathogenic?

CELF2 p.Lys508Thr (c.1523A>C) is classified Uncertain significance in CELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-12). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1.

How common is CELF2 p.Lys508Thr (c.1523A>C) in the general population?

CELF2 p.Lys508Thr (c.1523A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF2 p.Lys508Thr (c.1523A>C)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

CELF2 p.Lys508Thr

c.1523A>C · rs2550092400 · VCV3252695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic
REVEL	0.44	indeterminate
SaProt	LLR -15.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 7,704 bp · p 1.9e-16 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 K495T vs ClinVar K508T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CELF2
Protein: p.Lys508Thr
Coding: c.1523A>C
dbSNP: rs2550092400
Type: single nucleotide variant
Location: chr10:11329010 (GRCh38)

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

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-lys508thr (accessed [today's date]).

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