Is CELF5 p.Arg129His (c.386G>A) pathogenic?

CELF5 p.Arg129His (c.386G>A) is classified Uncertain significance in CELF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely benign (0.2951); Very rare (popmax 0.00446%, eas).

How common is CELF5 p.Arg129His (c.386G>A) in the general population?

CELF5 p.Arg129His (c.386G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CELF5 p.Arg129His (c.386G>A)?

AlphaMissense predicts likely benign (score 0.2951) — an in-silico prediction, not a clinical call.

CELF5 p.Arg129His

c.386G>A · VCV3490008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2951	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -10.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 49 kb · p 8.3e-09 · regional, not allelic
Overall
CADD	33.0	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 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000744% 12/1,613,454 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,440
Remaining individualsnot grpmax-eligible	0.0016%	62,450
Finnishnot grpmax-eligible	0.00156%	64,016
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000593%	168,507

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.Arg129His
Coding: c.386G>A
MANE Select: NM_021938
Type: single nucleotide variant
Location: chr19:3273915 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.74 · 1 PDB

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.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-arg129his (accessed [today's date]).

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