Is APAF1 p.Glu795Gln (c.2383G>C) pathogenic?

APAF1 p.Glu795Gln (c.2383G>C) is classified Uncertain significance in APAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-05-21). AlphaMissense: likely benign (0.1193); Rare (popmax 0.328%, amr); Associated with Inborn genetic diseases.

What condition is associated with APAF1 p.Glu795Gln (c.2383G>C)?

APAF1 p.Glu795Gln (c.2383G>C) is associated with Inborn genetic diseases (ClinVar).

How common is APAF1 p.Glu795Gln (c.2383G>C) in the general population?

APAF1 p.Glu795Gln (c.2383G>C) is rare (popmax 0.328%, amr) (gnomAD).

What do computational predictors say about APAF1 p.Glu795Gln (c.2383G>C)?

AlphaMissense predicts likely benign (score 0.1193) — an in-silico prediction, not a clinical call.

APAF1 p.Glu795Gln

c.2383G>C · rs181546874 · VCV520671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1193 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.328%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1193	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -7.34	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 8.3e-07 · regional, not allelic
Overall
CADD	23.9	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 0.328% Admixed American · 197/60,034 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.276%

Overall 0.0125% 201/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.328%	305
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,868
African / African-American	0.00133%	75,050

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: APAF1
Protein: p.Glu795Gln
Coding: c.2383G>C
MANE Select: NM_181861
dbSNP: rs181546874
Type: single nucleotide variant
Location: chr12:98699486 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 14 PDB

Full APAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APAF1 p.Arg750Lys Uncertain significance ★ ⚠ same condition
APAF1 c.2047-3T>C Benign ★★ same type
APAF1 p.Glu625Ala Benign ★★ same type
APAF1 p.Ser871Leu Likely benign ★★ ⚠ same type
APAF1 p.Thr446Ser Benign ★★ same type
APAF1 p.Tyr359= Benign ★★ same type
APAF1 p.Ala1025Val Uncertain significance ★ ⚠ same type
APAF1 p.Ala223Ser 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/apaf1-p-glu795gln (accessed [today's date]).

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