Is E2F5 p.Asn183Lys (c.549T>A) pathogenic?

E2F5 p.Asn183Lys (c.549T>A) is classified Uncertain significance in E2F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.138); Ultra-rare (popmax 0.012%, afr).

How common is E2F5 p.Asn183Lys (c.549T>A) in the general population?

E2F5 p.Asn183Lys (c.549T>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about E2F5 p.Asn183Lys (c.549T>A)?

AlphaMissense predicts likely benign (score 0.138) — an in-silico prediction, not a clinical call.

E2F5 p.Asn183Lys

c.549T>A · rs202172071 · VCV2361092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.138 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.138	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -3.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.052	GERP -2.4, phastCons 0.88
Regional constraint	o/e 0.90	unconstrained · MANE · 36 kb · p 0.039 · regional, not allelic
Overall
CADD	14.42	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

Grpmax group 0.012% African / African-American · 9/75,038 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000868% 14/1,613,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,338
Remaining individualsnot grpmax-eligible	0.0048%	20,823
Admixed American	0.00167%	59,986
European (non-Finnish)	8.48e-05%	1,179,439

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: E2F5
Protein: p.Asn183Lys
Coding: c.549T>A
MANE Select: NM_001951
dbSNP: rs202172071
Type: single nucleotide variant
Location: chr8:85206219 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.06 · 1 PDB
Residue 183: the 'dimerization' region

Full E2F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

E2F5 p.Ala192Ser Uncertain significance ★ ⚠ same type
E2F5 p.Ala295Glu Uncertain significance ★ ⚠ same type
E2F5 p.Ala44Thr Uncertain significance ★ ⚠ same type
E2F5 p.Ala44Val Uncertain significance ★ ⚠ same type
E2F5 p.Ala78Glu Uncertain significance ★ ⚠ same type
E2F5 p.Asp163Gly Uncertain significance ★ ⚠ same type
E2F5 p.Asp177Glu Uncertain significance ★ ⚠ same type
E2F5 p.Asp301Glu 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/e2f5-p-asn183lys (accessed [today's date]).

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