Is APOBEC4 p.Pro313Ser (c.937C>T) pathogenic?

APOBEC4 p.Pro313Ser (c.937C>T) is classified Uncertain significance in APOBEC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.3227); Ultra-rare (popmax 0.0657%, mid).

How common is APOBEC4 p.Pro313Ser (c.937C>T) in the general population?

APOBEC4 p.Pro313Ser (c.937C>T) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about APOBEC4 p.Pro313Ser (c.937C>T)?

AlphaMissense predicts likely benign (score 0.3227) — an in-silico prediction, not a clinical call.

APOBEC4 p.Pro313Ser

c.937C>T · VCV3934356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3227 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3227	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -6.47	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 8.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,100 bp · p 0.0016 · regional, not allelic
Overall
CADD	22.6	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

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00421% 68/1,614,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
South Asian	0.00549%	18,216
European (non-Finnish)	0.00466%	21,455
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	60,002
African / African-American	0.00134%	74,898

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.Pro313Ser
Coding: c.937C>T
MANE Select: NM_203454
Type: single nucleotide variant
Location: chr1:183647845 (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.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
APOBEC4 p.Arg335Ser 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-pro313ser (accessed [today's date]).

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