Is CELF4 p.Ala328= (c.984C>T) pathogenic?

CELF4 p.Ala328= (c.984C>T) is classified Benign in CELF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-18). Common (popmax 35.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with CELF4-related disorder.

What condition is associated with CELF4 p.Ala328= (c.984C>T)?

CELF4 p.Ala328= (c.984C>T) is associated with CELF4-related disorder (ClinVar).

CELF4 p.Ala328=

Q: How common is CELF4 p.Ala328= (c.984C>T) in the general population?

CELF4 p.Ala328= (c.984C>T) is common (popmax 35.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.984C>T · rs1443638 · VCV3060581

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 35.7%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

CELF4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.288	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -4.4
Overall
CADD	5.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.7% European (non-Finnish) · 421,138/1,179,132 alleles

Filtering AF 35.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.6%

Overall 32.9% 531,102/1,612,020 alleles · common exomes 487,559/1,459,850 · genomes 43,543/152,170 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	43.1%	2
Ashkenazi Jewishnot grpmax-eligible	41.3%	2
European (non-Finnish)grpmax	35.7%	3
Middle Eastern	32.7%	3
Remaining individualsnot grpmax-eligible	32.6%	3
Finnishnot grpmax-eligible	32.4%	3
East Asian	24.9%	4
South Asian	21.6%	5
Admixed American	18.3%	5
African / African-American	17%	6

Amish 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: CELF4
Protein: p.Ala328=
Coding: c.984C>T
MANE Select: NM_020180
dbSNP: rs1443638
Type: single nucleotide variant
Location: chr18:37270883 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.84 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 62.70 · 2 PDB

Full CELF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELF4-related disorder

Similar variants

CELF4 c.801+1G>C Uncertain significance ★ same condition
CELF4 p.Gln414His Uncertain significance ⚠ same condition
CELF4 c.801+7G>A Benign same condition
CELF4 p.Ala310= Likely benign same condition
CELF4 p.Asp69= Likely benign same condition
CELF4 p.Leu109= Likely benign same condition
CELF4 p.Phe358= Likely benign same condition
CELF4 p.Val279= Likely benign same condition

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/celf4-p-ala328 (accessed [today's date]).

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