Is ACP5 p.Ser258Arg (c.772A>C) pathogenic?

ACP5 p.Ser258Arg (c.772A>C) is classified Conflicting classifications of pathogenicity in ACP5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-01). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1.

How common is ACP5 p.Ser258Arg (c.772A>C) in the general population?

ACP5 p.Ser258Arg (c.772A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACP5 p.Ser258Arg (c.772A>C)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

ACP5 p.Ser258Arg

c.772A>C · rs2512719998 · VCV1708367

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic · top 1% in ACP5
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -14.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,304 bp · p 0.00091 · regional, not allelic
Overall
CADD	24.9	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

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: ACP5
Protein: p.Ser258Arg
Coding: c.772A>C
MANE Select: NM_001611
dbSNP: rs2512719998
Type: single nucleotide variant
Location: chr19:11575216 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.82 · 2 PDB
Residue 258: a β-strand

Full ACP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP5 p.Ser258fs Pathogenic/Likely pathogenic ★★ same residue
ACP5 p.Arg176Ter Pathogenic ★★ same type
ACP5 p.Gln184Ter Pathogenic/Likely pathogenic ★★ same type
ACP5 p.Gly109Arg Pathogenic/Likely pathogenic ★★ same type
ACP5 p.Met264Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
ACP5 p.Tyr123Ter Pathogenic ★★ same type
ACP5 p.Tyr246Ter Pathogenic/Likely pathogenic ★★ same type
ACP5 p.Tyr74Ter Pathogenic/Likely 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/acp5-p-ser258arg (accessed [today's date]).

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