Is APOBEC3D p.Trp145Ser (c.434G>C) pathogenic?

APOBEC3D p.Trp145Ser (c.434G>C) is classified Uncertain significance in APOBEC3D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.1122); Absent from gnomAD v4.1.

How common is APOBEC3D p.Trp145Ser (c.434G>C) in the general population?

APOBEC3D p.Trp145Ser (c.434G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOBEC3D p.Trp145Ser (c.434G>C)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

APOBEC3D p.Trp145Ser

c.434G>C · VCV4126366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -4.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.1	GERP -3.3
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	5.665	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOBEC3D
Protein: p.Trp145Ser
Coding: c.434G>C
MANE Select: NM_152426
Type: single nucleotide variant
Location: chr22:39025293 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.72
Residue 145: the cmp/dcmp-type deaminase 1 domain

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

Similar variants

APOBEC3D p.Trp145Cys Uncertain significance ★ ⚠ same residue
APOBEC3D p.Trp145Gly Uncertain significance ★ ⚠ same residue
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

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-trp145ser (accessed [today's date]).

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