Is CELF6 p.Phe178Leu (c.534T>G) pathogenic?

CELF6 p.Phe178Leu (c.534T>G) is classified Uncertain significance in CELF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is CELF6 p.Phe178Leu (c.534T>G) in the general population?

CELF6 p.Phe178Leu (c.534T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF6 p.Phe178Leu (c.534T>G)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

CELF6 p.Phe178Leu

c.534T>G · rs2505758779 · VCV2304789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 2% in CELF6
REVEL	0.265	benign-leaning
SaProt	LLR -13.04	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -4.8, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 30 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	21.8	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

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: CELF6
Protein: p.Phe178Leu
Coding: c.534T>G
MANE Select: NM_052840
dbSNP: rs2505758779
Type: single nucleotide variant
Location: chr15:72290008 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.19 · 1 PDB
Residue 178: the rrm 2 domain

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-phe178leu (accessed [today's date]).

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