Is CELF6 p.Ala344Asp (c.1031C>A) pathogenic?

CELF6 p.Ala344Asp (c.1031C>A) is classified Uncertain significance in CELF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: ambiguous (0.3776); Ultra-rare (popmax 0.0148%, nfe).

How common is CELF6 p.Ala344Asp (c.1031C>A) in the general population?

CELF6 p.Ala344Asp (c.1031C>A) is ultra-rare (popmax 0.0148%, nfe) (gnomAD).

What do computational predictors say about CELF6 p.Ala344Asp (c.1031C>A)?

AlphaMissense predicts ambiguous (score 0.3776) — an in-silico prediction, not a clinical call.

CELF6 p.Ala344Asp

c.1031C>A · rs201772134 · VCV3141956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3776 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3776	ambiguous
REVEL	0.481	indeterminate
SaProt	LLR -10.67	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,721 bp · p 0.007 · regional, not allelic
Overall
CADD	27.8	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 0.0148% European (non-Finnish) · 170/1,146,712 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.011% 171/1,550,258 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0148%	6,745
Remaining individualsnot grpmax-eligible	0.00166%	60,100

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: CELF6
Protein: p.Ala344Asp
Coding: c.1031C>A
MANE Select: NM_052840
dbSNP: rs201772134
Type: single nucleotide variant
Location: chr15:72288930 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.19 · 1 PDB

Full CELF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF6 p.Met40Thr Benign ★★ ⚠ same type
CELF6 p.Ala189Glu Uncertain significance ★ ⚠ same type
CELF6 p.Ala255Glu Uncertain significance ★ ⚠ same type
CELF6 p.Ala295Thr Uncertain significance ★ ⚠ same type
CELF6 p.Ala358Thr Uncertain significance ★ ⚠ same type
CELF6 p.Ala364Pro Uncertain significance ★ ⚠ same type
CELF6 p.Ala96Ser Uncertain significance ★ ⚠ same type
CELF6 p.Ala9Ser 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/celf6-p-ala344asp (accessed [today's date]).

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