Is CELF5 p.Arg117Trp (c.349C>T) pathogenic?

CELF5 p.Arg117Trp (c.349C>T) is classified Uncertain significance in CELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely pathogenic (0.8818); Very rare (popmax 0.000339%, nfe).

How common is CELF5 p.Arg117Trp (c.349C>T) in the general population?

CELF5 p.Arg117Trp (c.349C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CELF5 p.Arg117Trp (c.349C>T)?

AlphaMissense predicts likely pathogenic (score 0.8818) — an in-silico prediction, not a clinical call.

CELF5 p.Arg117Trp

c.349C>T · rs2080005478 · VCV2521208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8818	likely pathogenic
REVEL	0.279	benign-leaning
SaProt	LLR -15.20	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 4.8	GERP 0.63, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 49 kb · p 8.3e-09 · regional, not allelic
Overall
CADD	31.0	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 0.000339% European (non-Finnish) · 4/1,179,550 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,260 alleles · very rare

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.Arg117Trp
Coding: c.349C>T
MANE Select: NM_021938
dbSNP: rs2080005478
Type: single nucleotide variant
Location: chr19:3273878 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 117: the rrm 1 domain

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

Similar variants

CELF5 p.Gln364Pro Uncertain significance ★★ ⚠ same type
CELF5 p.Ala309Thr Uncertain significance ★ ⚠ same type
CELF5 p.Ala373Val 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
CELF5 p.Gln155Leu 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-arg117trp (accessed [today's date]).

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