Is CELF3 p.Val169Met (c.505G>A) pathogenic?

CELF3 p.Val169Met (c.505G>A) is classified Uncertain significance in CELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely pathogenic (0.9619); Absent from gnomAD v4.1.

How common is CELF3 p.Val169Met (c.505G>A) in the general population?

CELF3 p.Val169Met (c.505G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF3 p.Val169Met (c.505G>A)?

AlphaMissense predicts likely pathogenic (score 0.9619) — an in-silico prediction, not a clinical call.

CELF3 p.Val169Met

c.505G>A · VCV3489995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9619 · 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	0.9619	likely pathogenic
REVEL	0.367	indeterminate
SaProt	LLR -13.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 8,731 bp · p 6.5e-15 · regional, not allelic
Overall
CADD	27.6	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.

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: CELF3
Protein: p.Val169Met
Coding: c.505G>A
MANE Select: NM_007185
Type: single nucleotide variant
Location: chr1:151707917 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 1 PDB
Residue 169: the rrm 2 domain

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.Ala312Val Uncertain significance ★ ⚠ same type
CELF3 p.Ala323Thr 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-val169met (accessed [today's date]).

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