Is APOBEC3C p.His64Pro (c.191A>C) pathogenic?

APOBEC3C p.His64Pro (c.191A>C) is classified Likely benign in APOBEC3C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0173%, nfe).

How common is APOBEC3C p.His64Pro (c.191A>C) in the general population?

APOBEC3C p.His64Pro (c.191A>C) is ultra-rare (popmax 0.0173%, nfe) (gnomAD).

What do computational predictors say about APOBEC3C p.His64Pro (c.191A>C)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

APOBEC3C p.His64Pro

c.191A>C · rs370965070 · VCV2370464

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -3.13	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 -9.8	GERP -2.3
Regional constraint	o/e 1.01	unconstrained · MANE · 4,021 bp · p 0.89 · regional, not allelic
Overall
CADD	0.006	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 0.0173% European (non-Finnish) · 204/1,179,340 alleles

Filtering AF 0.0153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.013% 209/1,613,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0173%	5,781
Remaining individualsnot grpmax-eligible	0.00801%	12,490

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: APOBEC3C
Protein: p.His64Pro
Coding: c.191A>C
MANE Select: NM_014508
dbSNP: rs370965070
Type: single nucleotide variant
Location: chr22:39017782 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.29 · 2 PDB
Residue 64: the cmp/dcmp-type deaminase domain; the '(microbial infection) required for interaction with human foamy virus protein bet' region; an α-helix

Full APOBEC3C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3C p.Ser188Ile Benign ★★ same type
APOBEC3C p.Arg186Trp Uncertain significance ★ ⚠ same type
APOBEC3C p.Arg30Trp Uncertain significance ★ ⚠ same type
APOBEC3C p.Asn165Lys Uncertain significance ★ ⚠ same type
APOBEC3C p.Asp78Glu Uncertain significance ★ ⚠ same type
APOBEC3C p.Cys36Arg Uncertain significance ★ ⚠ same type
APOBEC3C p.Cys70Trp Uncertain significance ★ ⚠ same type
APOBEC3C p.Glu146Gln 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/apobec3c-p-his64pro (accessed [today's date]).

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