Is CELF5 p.Val314Met (c.940G>A) pathogenic?

CELF5 p.Val314Met (c.940G>A) is classified Uncertain significance in CELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0954); Ultra-rare (popmax 0.0517%, nfe).

How common is CELF5 p.Val314Met (c.940G>A) in the general population?

CELF5 p.Val314Met (c.940G>A) is ultra-rare (popmax 0.0517%, nfe) (gnomAD).

What do computational predictors say about CELF5 p.Val314Met (c.940G>A)?

AlphaMissense predicts likely benign (score 0.0954) — an in-silico prediction, not a clinical call.

CELF5 p.Val314Met

c.940G>A · rs200977944 · VCV2362207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0954	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.44	acceptor gain · deltas
Pangolin	Δ0.22	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.5	GERP -0.89, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,783 bp · p 0.7 · regional, not allelic
Overall
CADD	26.4	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 0.0517% European (non-Finnish) · 610/1,180,032 alleles

Filtering AF 0.0483% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0469%

Overall 0.0412% 665/1,612,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0592%	1,688
European (non-Finnish)grpmax	0.0517%	1,934
African / African-American	0.0107%	9,368
East Asian	0.00668%	14,965
Finnishnot grpmax-eligible	0.00483%	20,717
Admixed American	0.00333%	30,006
South Asian	0.0022%	45,545

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CELF5
Protein: p.Val314Met
Coding: c.940G>A
MANE Select: NM_021938
dbSNP: rs200977944
Type: single nucleotide variant
Location: chr19:3282399 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB

Full CELF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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CELF5 p.Ala309Thr Uncertain significance ★ ⚠ same type
CELF5 p.Ala373Val Uncertain significance ★ ⚠ same type
CELF5 p.Arg117Trp Uncertain significance ★ ⚠ same type
CELF5 p.Arg129His Uncertain significance ★ ⚠ same type
CELF5 p.Arg218Leu Uncertain significance ★ ⚠ same type
CELF5 p.Gln12Arg Uncertain significance ★ ⚠ same type
CELF5 p.Gln13Leu 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/celf5-p-val314met (accessed [today's date]).

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