Is E4F1 p.Ala728Ser (c.2182G>T) pathogenic?

E4F1 p.Ala728Ser (c.2182G>T) is classified Uncertain significance in E4F1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.3134); Absent from gnomAD v4.1.

How common is E4F1 p.Ala728Ser (c.2182G>T) in the general population?

E4F1 p.Ala728Ser (c.2182G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about E4F1 p.Ala728Ser (c.2182G>T)?

AlphaMissense predicts likely benign (score 0.3134) — an in-silico prediction, not a clinical call.

E4F1 p.Ala728Ser

c.2182G>T · VCV3274319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3134 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,640)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3134	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,400 bp · p 0.81 · regional, not allelic
Overall
CADD	25.3	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

No allele count reported in gnomAD v4.1 (AN 1,611,640). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: E4F1
Protein: p.Ala728Ser
Coding: c.2182G>T
MANE Select: NM_004424
Type: single nucleotide variant
Location: chr16:2235399 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.68

Full E4F1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E4F1 p.Arg490His Uncertain significance ★★ ⚠ same type
E4F1 p.Lys144Gln Likely pathogenic ★ ⚠ same type
E4F1 p.Ala124Val Uncertain significance ★ ⚠ same type
E4F1 p.Ala152Val Uncertain significance ★ ⚠ same type
E4F1 p.Ala15Thr Uncertain significance ★ ⚠ same type
E4F1 p.Ala21Asp Uncertain significance ★ ⚠ same type
E4F1 p.Ala21Ser Uncertain significance ★ ⚠ same type
E4F1 p.Ala292Thr 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/e4f1-p-ala728ser (accessed [today's date]).

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