Is ACP7 p.Arg181His (c.542G>A) pathogenic?

ACP7 p.Arg181His (c.542G>A) is classified Uncertain significance in ACP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1429); Very rare (popmax 0.00878%, sas).

How common is ACP7 p.Arg181His (c.542G>A) in the general population?

ACP7 p.Arg181His (c.542G>A) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about ACP7 p.Arg181His (c.542G>A)?

AlphaMissense predicts likely benign (score 0.1429) — an in-silico prediction, not a clinical call.

ACP7 p.Arg181His

c.542G>A · rs754476691 · VCV3139136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1429	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 25 kb · p 0.36 · regional, not allelic
Overall
CADD	24.4	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 0.00878% South Asian · 8/91,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00297% 48/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,386
Admixed American	0.00667%	14,993
East Asian	0.00446%	22,435
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.00263%	38,066
African / African-American	0.00134%	74,906

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: ACP7
Protein: p.Arg181His
Coding: c.542G>A
MANE Select: NM_001004318
dbSNP: rs754476691
Type: single nucleotide variant
Location: chr19:39100263 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.97

Full ACP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP7 p.Gly396Arg Uncertain significance ★ ⚠ same type
ACP7 p.Leu256Ser 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/acp7-p-arg181his (accessed [today's date]).

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