Is CELF6 p.Cys243Phe (c.728G>T) pathogenic?

CELF6 p.Cys243Phe (c.728G>T) is classified Uncertain significance in CELF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.1074); Ultra-rare (popmax 0.0103%, eas).

How common is CELF6 p.Cys243Phe (c.728G>T) in the general population?

CELF6 p.Cys243Phe (c.728G>T) is ultra-rare (popmax 0.0103%, eas) (gnomAD).

What do computational predictors say about CELF6 p.Cys243Phe (c.728G>T)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

CELF6 p.Cys243Phe

c.728G>T · rs1189044614 · VCV2467012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -1.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -3.4, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 2,721 bp · p 0.007 · regional, not allelic
Overall
CADD	20.9	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 0.0103% East Asian · 4/38,794 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00212%

Overall 0.000666% 9/1,350,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0103%	9,698
Remaining individualsnot grpmax-eligible	0.00687%	14,560
South Asian	0.00124%	80,602

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.Cys243Phe
Coding: c.728G>T
MANE Select: NM_052840
dbSNP: rs1189044614
Type: single nucleotide variant
Location: chr15:72289646 (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.Ala344Asp 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

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-cys243phe (accessed [today's date]).

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