Is CELF6 p.Pro169Thr (c.505C>A) pathogenic?

CELF6 p.Pro169Thr (c.505C>A) is classified Uncertain significance in CELF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1114); Absent from gnomAD v4.1.

How common is CELF6 p.Pro169Thr (c.505C>A) in the general population?

CELF6 p.Pro169Thr (c.505C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELF6 p.Pro169Thr (c.505C>A)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

CELF6 p.Pro169Thr

c.505C>A · VCV3490018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -11.95	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 30 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	24.6	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.Pro169Thr
Coding: c.505C>A
MANE Select: NM_052840
Type: single nucleotide variant
Location: chr15:72290145 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.19 · 1 PDB
Residue 169: the rrm 2 domain

Full CELF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF6 p.Pro169Arg Uncertain significance ★ ⚠ same residue
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

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-pro169thr (accessed [today's date]).

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