Is ACP4 p.Val141Ala (c.422T>C) pathogenic?

ACP4 p.Val141Ala (c.422T>C) is classified Uncertain significance in ACP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.7259); Absent from gnomAD v4.1.

How common is ACP4 p.Val141Ala (c.422T>C) in the general population?

ACP4 p.Val141Ala (c.422T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACP4 p.Val141Ala (c.422T>C)?

AlphaMissense predicts likely pathogenic (score 0.7259) — an in-silico prediction, not a clinical call.

ACP4 p.Val141Ala

c.422T>C · VCV4217829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7259 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7259	likely pathogenic
REVEL	0.365	indeterminate
SaProt	LLR -11.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 4,740 bp · p 0.54 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACP4
Protein: p.Val141Ala
Coding: c.422T>C
MANE Select: NM_033068
Type: single nucleotide variant
Location: chr19:50791774 (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-val141ala (accessed [today's date]).

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