Is ACP2 p.Gln248Arg (c.743A>G) pathogenic?

ACP2 p.Gln248Arg (c.743A>G) is classified Uncertain significance in ACP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.055); Ultra-rare (popmax 0.0367%, amr).

How common is ACP2 p.Gln248Arg (c.743A>G) in the general population?

ACP2 p.Gln248Arg (c.743A>G) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

What do computational predictors say about ACP2 p.Gln248Arg (c.743A>G)?

AlphaMissense predicts likely benign (score 0.055) — an in-silico prediction, not a clinical call.

ACP2 p.Gln248Arg

c.743A>G · rs757302233 · VCV2338372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.055 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.055	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -4.29	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 2.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 8,670 bp · p 0.0021 · regional, not allelic
Overall
CADD	19.64	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 0.0367% Admixed American · 22/59,866 alleles

Filtering AF 0.0249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00801% 129/1,611,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,721
European (non-Finnish)	0.00857%	11,665
Remaining individualsnot grpmax-eligible	0.00802%	12,472
East Asian	0.00223%	44,806

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: ACP2
Protein: p.Gln248Arg
Coding: c.743A>G
MANE Select: NM_001610
dbSNP: rs757302233
Type: single nucleotide variant
Location: chr11:47244764 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09
Residue 248: a disulfide bond

Full ACP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP2 c.856-4G>A Benign ★★ same type
ACP2 p.Arg10Trp Likely benign ★★ same type
ACP2 p.Phe393Leu Benign/Likely benign ★★ same type
ACP2 p.Val416= Benign ★★ same type
ACP2 p.Ala11Glu Uncertain significance ★ ⚠ same type
ACP2 p.Ala272Val Uncertain significance ★ ⚠ same type
ACP2 p.Ala336Thr Uncertain significance ★ ⚠ same type
ACP2 p.Ala336Val 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/acp2-p-gln248arg (accessed [today's date]).

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