Is CELF3 p.Arg112Gln (c.335G>A) pathogenic?

CELF3 p.Arg112Gln (c.335G>A) is classified Uncertain significance in CELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.1069); Very rare (popmax 0.00161%, nfe).

How common is CELF3 p.Arg112Gln (c.335G>A) in the general population?

CELF3 p.Arg112Gln (c.335G>A) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about CELF3 p.Arg112Gln (c.335G>A)?

AlphaMissense predicts likely benign (score 0.1069) — an in-silico prediction, not a clinical call.

CELF3 p.Arg112Gln

c.335G>A · rs1018636842 · VCV2378494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1069	likely benign
REVEL	0.771	pathogenic-leaning
SaProt	LLR -11.65	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 8,731 bp · p 6.5e-15 · regional, not allelic
Overall
CADD	28.6	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

Grpmax group 0.00161% European (non-Finnish) · 19/1,179,980 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00167% 27/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00937%	10,673
European (non-Finnish)grpmax	0.00161%	62,104
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,902

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CELF3
Protein: p.Arg112Gln
Coding: c.335G>A
MANE Select: NM_007185
dbSNP: rs1018636842
Type: single nucleotide variant
Location: chr1:151709291 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 1 PDB
Residue 112: an α-helix; the rrm 2 domain

Full CELF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF3 p.Ala146Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala206Ser Uncertain significance ★ ⚠ same type
CELF3 p.Ala206Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala216Glu Uncertain significance ★ ⚠ same type
CELF3 p.Ala221Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala276Thr Uncertain significance ★ ⚠ same type
CELF3 p.Ala312Val Uncertain significance ★ ⚠ same type
CELF3 p.Ala323Thr 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/celf3-p-arg112gln (accessed [today's date]).

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