Is APOBEC3G p.His72Asp (c.214C>G) pathogenic?

APOBEC3G p.His72Asp (c.214C>G) is classified Uncertain significance in APOBEC3G (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely benign (0.1575); Very rare (popmax 0.00441%, nfe).

How common is APOBEC3G p.His72Asp (c.214C>G) in the general population?

APOBEC3G p.His72Asp (c.214C>G) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about APOBEC3G p.His72Asp (c.214C>G)?

AlphaMissense predicts likely benign (score 0.1575) — an in-silico prediction, not a clinical call.

APOBEC3G p.His72Asp

c.214C>G · rs138285438 · VCV2592903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1575	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.22	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 -6.1	GERP -3.7
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.3 · regional, not allelic
Overall
CADD	0.013	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 0.00441% European (non-Finnish) · 52/1,180,022 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00353% 57/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,693
Admixed American	0.00333%	29,988
Remaining individualsnot grpmax-eligible	0.0032%	31,242
South Asian	0.0011%	91,076

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: APOBEC3G
Protein: p.His72Asp
Coding: c.214C>G
MANE Select: NM_021822
dbSNP: rs138285438
Type: single nucleotide variant
Location: chr22:39080975 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57 · 22 PDB
Residue 72: the cmp/dcmp-type deaminase 1 domain; an α-helix

Full APOBEC3G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3G p.Ala134Val Uncertain significance ★ ⚠ same type
APOBEC3G p.Ala312Val Uncertain significance ★ ⚠ same type
APOBEC3G p.Ala333Asp Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg122Cys Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg136Cys Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg30Trp Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg313His Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg326Cys 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/apobec3g-p-his72asp (accessed [today's date]).

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