Is CELF5 p.Pro31Ser (c.91C>T) pathogenic?

CELF5 p.Pro31Ser (c.91C>T) is classified Uncertain significance in CELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0338%, mid).

How common is CELF5 p.Pro31Ser (c.91C>T) in the general population?

CELF5 p.Pro31Ser (c.91C>T) is ultra-rare (popmax 0.0338%, mid) (gnomAD).

What do computational predictors say about CELF5 p.Pro31Ser (c.91C>T)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

CELF5 p.Pro31Ser

c.91C>T · rs759584916 · VCV2313382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0338%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.24	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 4.8	GERP 0.004, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 106 bp · p 0.22 · regional, not allelic
Overall
CADD	18.53	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 0.0338% Middle Eastern · 2/5,912 alleles

Filtering AF 0.00595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00247%

Overall 0.00154% 22/1,429,718 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0338%	2,956
Admixed American	0.00364%	27,498
Remaining individualsnot grpmax-eligible	0.00327%	30,605
European (non-Finnish)	0.00137%	72,822

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.Pro31Ser
Coding: c.91C>T
MANE Select: NM_021938
dbSNP: rs759584916
Type: single nucleotide variant
Location: chr19:3224830 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB
Residue 31: the 'disordered' region

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.Arg117Trp 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

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-pro31ser (accessed [today's date]).

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