Is ACP2 p.Arg10Trp (c.28C>T) pathogenic?

ACP2 p.Arg10Trp (c.28C>T) is classified Likely benign in ACP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-08). AlphaMissense: likely benign (0.1257); Rare (popmax 0.271%, nfe).

How common is ACP2 p.Arg10Trp (c.28C>T) in the general population?

ACP2 p.Arg10Trp (c.28C>T) is rare (popmax 0.271%, nfe) (gnomAD).

What do computational predictors say about ACP2 p.Arg10Trp (c.28C>T)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

ACP2 p.Arg10Trp

c.28C>T · rs41275182 · VCV786418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.56	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 1.5	GERP -2.5, phastCons 0.02
Regional constraint	o/e 0.87	unconstrained · MANE · 8,670 bp · p 0.0021 · regional, not allelic
Overall
CADD	16.43	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 0.271% European (non-Finnish) · 3,188/1,174,224 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.26%

Overall 0.236% 3,773/1,601,376 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.65%	154
European (non-Finnish)grpmax	0.271%	368
Remaining individualsnot grpmax-eligible	0.194%	516
Admixed American	0.0584%	1,711
Middle Eastern	0.0496%	2,015
African / African-American	0.024%	4,163
Ashkenazi Jewishnot grpmax-eligible	0.00682%	14,654
South Asian	0.00113%	88,824

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg10Trp
Coding: c.28C>T
MANE Select: NM_001610
dbSNP: rs41275182
Type: single nucleotide variant
Location: chr11:47248762 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.09

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.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
ACP2 p.Arg109Trp 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-arg10trp (accessed [today's date]).

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