Is APOBEC3D p.Cys320Arg (c.958T>C) pathogenic?

APOBEC3D p.Cys320Arg (c.958T>C) is classified Uncertain significance in APOBEC3D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.3481); Very rare (popmax 8.47e-05%, nfe).

How common is APOBEC3D p.Cys320Arg (c.958T>C) in the general population?

APOBEC3D p.Cys320Arg (c.958T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about APOBEC3D p.Cys320Arg (c.958T>C)?

AlphaMissense predicts ambiguous (score 0.3481) — an in-silico prediction, not a clinical call.

APOBEC3D p.Cys320Arg

c.958T>C · VCV4126344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3481 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3481	ambiguous
REVEL	0.124	moderately benign-leaning
SaProt	LLR -8.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP 0.5, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	15.08	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 8.47e-05% European (non-Finnish) · 1/1,180,050 alleles

Overall 0.000657% 1/152,208 alleles · very rare

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.Cys320Arg
Coding: c.958T>C
MANE Select: NM_152426
Type: single nucleotide variant
Location: chr22:39031889 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.72
Residue 320: the cmp/dcmp-type deaminase 2 domain

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-cys320arg (accessed [today's date]).

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