Is ACSM2B p.Val394Asp (c.1181T>A) pathogenic?

ACSM2B p.Val394Asp (c.1181T>A) is classified Uncertain significance in ACSM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely pathogenic (0.9299); Very rare (popmax 6.85e-05%).

How common is ACSM2B p.Val394Asp (c.1181T>A) in the general population?

ACSM2B p.Val394Asp (c.1181T>A) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about ACSM2B p.Val394Asp (c.1181T>A)?

AlphaMissense predicts likely pathogenic (score 0.9299) — an in-silico prediction, not a clinical call.

ACSM2B p.Val394Asp

c.1181T>A · rs2548900616 · VCV2320561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9299	likely pathogenic · top 2% in ACSM2B
REVEL	0.412	indeterminate
SaProt	LLR -16.64	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 7.4	GERP 1.7, phastCons 0.93
Regional constraint	o/e 0.97	unconstrained · MANE · 28 kb · p 0.38 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,562 alleles · very rare

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: ACSM2B
Protein: p.Val394Asp
Coding: c.1181T>A
MANE Select: NM_001105069
dbSNP: rs2548900616
Type: single nucleotide variant
Location: chr16:20545257 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.41

Full ACSM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM2B p.Val394Ile Uncertain significance ★ ⚠ same residue
ACSM2B p.Ile305Val Benign ★★ same type
ACSM2B p.Pro312= Benign ★★ same type
ACSM2B p.Ser272= Benign ★★ same type
ACSM2B p.Ala231Ser Uncertain significance ★ ⚠ same type
ACSM2B p.Ala387Val Uncertain significance ★ ⚠ same type
ACSM2B p.Ala487Asp Uncertain significance ★ ⚠ same type
ACSM2B p.Arg148Lys 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/acsm2b-p-val394asp (accessed [today's date]).

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