Is CELF4 p.Gly343Ser (c.1027G>A) pathogenic?

CELF4 p.Gly343Ser (c.1027G>A) is classified Likely benign in CELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.0856); Ultra-rare (popmax 0.0602%, eas).

How common is CELF4 p.Gly343Ser (c.1027G>A) in the general population?

CELF4 p.Gly343Ser (c.1027G>A) is ultra-rare (popmax 0.0602%, eas) (gnomAD).

What do computational predictors say about CELF4 p.Gly343Ser (c.1027G>A)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

CELF4 p.Gly343Ser

c.1027G>A · rs773175289 · VCV2535776

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0602%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 21 kb · p 4.4e-06 · 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 0.0602% East Asian · 27/44,882 alleles

Filtering AF 0.0424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.0039% 63/1,613,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0602%	1,662
Remaining individualsnot grpmax-eligible	0.0032%	31,235
African / African-American	0.00267%	37,465
European (non-Finnish)	0.00263%	38,064
Finnishnot grpmax-eligible	0.00157%	63,766

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: CELF4
Protein: p.Gly343Ser
Coding: c.1027G>A
MANE Select: NM_020180
dbSNP: rs773175289
Type: single nucleotide variant
Location: chr18:37270840 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB

Full CELF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF4 p.Gly193Val Uncertain significance ★★ ⚠ same type
CELF4 p.Ala381= Benign/Likely benign ★★ same type
CELF4 p.Pro127= Benign ★★ same type
CELF4 p.Pro406= Benign ★★ same type
CELF4 p.Glu76Ter Pathogenic ★ same type
CELF4 c.1165+2T>C Uncertain significance ★ same type
CELF4 c.370-67640C>A Uncertain significance ★ same type
CELF4 c.577+2T>G 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/celf4-p-gly343ser (accessed [today's date]).

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