Is APOBEC4 p.Ile202Val (c.604A>G) pathogenic?

APOBEC4 p.Ile202Val (c.604A>G) is classified Likely benign in APOBEC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0498); Ultra-rare (popmax 0.0428%, sas).

How common is APOBEC4 p.Ile202Val (c.604A>G) in the general population?

APOBEC4 p.Ile202Val (c.604A>G) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

What do computational predictors say about APOBEC4 p.Ile202Val (c.604A>G)?

AlphaMissense predicts likely benign (score 0.0498) — an in-silico prediction, not a clinical call.

APOBEC4 p.Ile202Val

c.604A>G · VCV4126581

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0498 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0498	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -2.85	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 3.9	GERP 0.59, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,100 bp · p 0.0016 · regional, not allelic
Overall
CADD	5.144	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 0.0428% South Asian · 39/91,088 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00254% 41/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,336
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.47e-05%	1,180,048

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: APOBEC4
Protein: p.Ile202Val
Coding: c.604A>G
MANE Select: NM_203454
Type: single nucleotide variant
Location: chr1:183648178 (GRCh38)
Gene constraint: LOEUF 1.412 · pLI 0.52 (gnomAD)
Structure: AlphaFold pLDDT 71.60

Full APOBEC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC4 p.Ile202Thr Uncertain significance ★ ⚠ same residue
APOBEC4 p.Asn321Asp Benign ★★ same type
APOBEC4 p.Pro182= Benign ★★ same type
APOBEC4 p.Ser196Cys Benign ★★ ⚠ same type
APOBEC4 p.Ala231Asp Uncertain significance ★ ⚠ same type
APOBEC4 p.Arg175Gln Uncertain significance ★ ⚠ same type
APOBEC4 p.Arg175Trp Uncertain significance ★ ⚠ same type
APOBEC4 p.Arg318Lys 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/apobec4-p-ile202val (accessed [today's date]).

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