Is ACMSD p.His8Arg (c.23A>G) pathogenic?

ACMSD p.His8Arg (c.23A>G) is classified Uncertain significance in ACMSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.9752); Absent from gnomAD v4.1.

How common is ACMSD p.His8Arg (c.23A>G) in the general population?

ACMSD p.His8Arg (c.23A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACMSD p.His8Arg (c.23A>G)?

AlphaMissense predicts likely pathogenic (score 0.9752) — an in-silico prediction, not a clinical call.

ACMSD p.His8Arg

c.23A>G · VCV3998690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9752	likely pathogenic · top 3% in ACMSD
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -14.83	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 9.3	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 63 kb · p 0.52 · regional, not allelic
Overall
CADD	25.4	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: ACMSD
Protein: p.His8Arg
Coding: c.23A>G
MANE Select: NM_138326
Type: single nucleotide variant
Location: chr2:134838705 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.67 · 6 PDB
Residue 8: a binding site; a β-strand

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

Similar variants

ACMSD p.Pro11= Benign ★★ same type
ACMSD c.677-14G>T Uncertain significance ★ same type
ACMSD c.948+1G>A Uncertain significance ★ same type
ACMSD p.Ala101Thr Uncertain significance ★ ⚠ same type
ACMSD p.Ala121Val Uncertain significance ★ ⚠ same type
ACMSD p.Ala154Val Uncertain significance ★ ⚠ same type
ACMSD p.Ala162Val Uncertain significance ★ ⚠ same type
ACMSD p.Ala223Thr 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/acmsd-p-his8arg (accessed [today's date]).

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