Is APOBEC3H p.Ile96Val (c.286A>G) pathogenic?

APOBEC3H p.Ile96Val (c.286A>G) is classified Uncertain significance in APOBEC3H (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). AlphaMissense: likely benign (0.1164); Very rare (popmax 0.00502%, amr).

How common is APOBEC3H p.Ile96Val (c.286A>G) in the general population?

APOBEC3H p.Ile96Val (c.286A>G) is very rare (popmax 0.00502%, amr) (gnomAD).

What do computational predictors say about APOBEC3H p.Ile96Val (c.286A>G)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

APOBEC3H p.Ile96Val

c.286A>G · VCV3886147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00502%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -4.90	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 -1.1	GERP -2.8
Regional constraint	o/e 1.00	unconstrained · MANE · 3,415 bp · p 0.95 · regional, not allelic
Overall
CADD	0.002	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 0.00502% Admixed American · 3/59,808 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000274% 4/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00502%	19,936
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: APOBEC3H
Protein: p.Ile96Val
Coding: c.286A>G
MANE Select: NM_181773
Type: single nucleotide variant
Location: chr22:39101372 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 89.41 · 4 PDB
Residue 96: the cmp/dcmp-type deaminase domain; an α-helix

Full APOBEC3H gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3H p.Phe107= Benign ★★ same type
APOBEC3H p.Arg10Cys Uncertain significance ★ ⚠ same type
APOBEC3H p.Arg10His Uncertain significance ★ ⚠ same type
APOBEC3H p.Arg110His Uncertain significance ★ ⚠ same type
APOBEC3H p.Arg17Cys Uncertain significance ★ ⚠ same type
APOBEC3H p.Arg17His Uncertain significance ★ ⚠ same type
APOBEC3H p.Cys116Trp Uncertain significance ★ ⚠ same type
APOBEC3H p.Glu146Gly 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/apobec3h-p-ile96val (accessed [today's date]).

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