Is E2F3 p.Ala401Ser (c.1201G>T) pathogenic?

E2F3 p.Ala401Ser (c.1201G>T) is classified Likely benign in E2F3 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2023-04-04). AlphaMissense: likely benign (0.1); Rare (popmax 0.291%, nfe); Associated with E2F3-related disorder.

What condition is associated with E2F3 p.Ala401Ser (c.1201G>T)?

E2F3 p.Ala401Ser (c.1201G>T) is associated with E2F3-related disorder (ClinVar).

How common is E2F3 p.Ala401Ser (c.1201G>T) in the general population?

E2F3 p.Ala401Ser (c.1201G>T) is rare (popmax 0.291%, nfe) (gnomAD).

What do computational predictors say about E2F3 p.Ala401Ser (c.1201G>T)?

AlphaMissense predicts likely benign (score 0.1) — an in-silico prediction, not a clinical call.

E2F3 p.Ala401Ser

c.1201G>T · rs151305307 · VCV3039257

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.291%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

E2F3-related disorder

Computational evidence

Protein change
AlphaMissense	0.1	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP 1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 7,665 bp · p 0.01 · regional, not allelic
Overall
CADD	19.59	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 0.291% European (non-Finnish) · 3,428/1,179,976 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.279%

Overall 0.224% 3,617/1,614,008 alleles · rare exomes 3,372/1,461,802 · genomes 245/152,206 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.31%	43
European (non-Finnish)grpmax	0.291%	344
Remaining individualsnot grpmax-eligible	0.117%	856
Finnishnot grpmax-eligible	0.0562%	1,778
African / African-American	0.056%	1,786
Admixed American	0.0267%	3,750
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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: E2F3
Protein: p.Ala401Ser
Coding: c.1201G>T
MANE Select: NM_001949
dbSNP: rs151305307
Type: single nucleotide variant
Location: chr6:20490233 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.16
Residue 401: the 'transactivation' region

Full E2F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

E2F3-related disorder

Similar variants

E2F3 p.Asp389Asn Benign ★★ same type
E2F3 p.Ala404Ser Uncertain significance ★ ⚠ same type
E2F3 p.Ala450Gly Uncertain significance ★ ⚠ same type
E2F3 p.Ala8Ser Uncertain significance ★ ⚠ same type
E2F3 p.Arg121Cys Uncertain significance ★ ⚠ same type
E2F3 p.Arg305Gln Uncertain significance ★ same type
E2F3 p.Asn369Asp Uncertain significance ★ ⚠ same type
E2F3 p.Asn396His 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/e2f3-p-ala401ser (accessed [today's date]).

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