Is ACP4 p.Pro10Arg (c.29C>G) pathogenic?

ACP4 p.Pro10Arg (c.29C>G) is classified Uncertain significance in ACP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.0541); Ultra-rare (popmax 0.0932%, nfe).

How common is ACP4 p.Pro10Arg (c.29C>G) in the general population?

ACP4 p.Pro10Arg (c.29C>G) is ultra-rare (popmax 0.0932%, nfe) (gnomAD).

What do computational predictors say about ACP4 p.Pro10Arg (c.29C>G)?

AlphaMissense predicts likely benign (score 0.0541) — an in-silico prediction, not a clinical call.

ACP4 p.Pro10Arg

c.29C>G · VCV4217851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0541 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0541	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.57	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 0.1	GERP -3.4
Regional constraint	o/e 1.03	unconstrained · MANE · 4,740 bp · p 0.54 · regional, not allelic
Overall
CADD	15.6	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 0.0932% European (non-Finnish) · 1,091/1,170,200 alleles

Filtering AF 0.0886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0868%

Overall 0.0728% 1,156/1,587,294 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0932%	1,073
Remaining individualsnot grpmax-eligible	0.0666%	1,501
African / African-American	0.0161%	6,223
Admixed American	0.0159%	6,282
Finnishnot grpmax-eligible	0.00518%	19,312

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: ACP4
Protein: p.Pro10Arg
Coding: c.29C>G
MANE Select: NM_033068
Type: single nucleotide variant
Location: chr19:50790443 (GRCh38)
Gene constraint: LOEUF 1.413 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.30

Full ACP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP4 p.Arg111Cys Pathogenic/Likely pathogenic ★★ same type
ACP4 c.550-4C>T Benign ★★ same type
ACP4 c.550-9C>T Benign ★★ same type
ACP4 p.Gly328Ala Benign ★★ same type
ACP4 p.Pro125= Benign ★★ same type
ACP4 c.645+1G>A Likely pathogenic ★ same type
ACP4 p.Leu85Pro Pathogenic ★ same type
ACP4 p.Met282Thr Pathogenic ★ ⚠ 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/acp4-p-pro10arg (accessed [today's date]).

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