Is APOBEC3D p.Cys293Phe (c.878G>T) pathogenic?

APOBEC3D p.Cys293Phe (c.878G>T) is classified Uncertain significance in APOBEC3D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.4432); Very rare (popmax 0.00267%, afr).

How common is APOBEC3D p.Cys293Phe (c.878G>T) in the general population?

APOBEC3D p.Cys293Phe (c.878G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about APOBEC3D p.Cys293Phe (c.878G>T)?

AlphaMissense predicts ambiguous (score 0.4432) — an in-silico prediction, not a clinical call.

APOBEC3D p.Cys293Phe

c.878G>T · VCV4641710

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.4432	ambiguous
REVEL	0.53	indeterminate
SaProt	LLR -7.54	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	22.1	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 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 21/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,458
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00153%	65,557

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: APOBEC3D
Protein: p.Cys293Phe
Coding: c.878G>T
MANE Select: NM_152426
Type: single nucleotide variant
Location: chr22:39031809 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.72
Residue 293: the cmp/dcmp-type deaminase 2 domain; a binding site

Full APOBEC3D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3D p.Ala121Ser Uncertain significance ★ ⚠ same type
APOBEC3D p.Ala133Thr Uncertain significance ★ ⚠ same type
APOBEC3D p.Ala191Thr Uncertain significance ★ ⚠ same type
APOBEC3D p.Ala263Val Uncertain significance ★ ⚠ same type
APOBEC3D p.Ala305Val Uncertain significance ★ ⚠ same type
APOBEC3D p.Ala79Pro Uncertain significance ★ ⚠ same type
APOBEC3D p.Arg11Gln Uncertain significance ★ ⚠ same type
APOBEC3D p.Arg134Cys 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/apobec3d-p-cys293phe (accessed [today's date]).

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