Is ACSM6 p.Val45Ala (c.134T>C) pathogenic?

ACSM6 p.Val45Ala (c.134T>C) is classified Uncertain significance in ACSM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). AlphaMissense: likely benign (0.0986); Absent from gnomAD v4.1.

How common is ACSM6 p.Val45Ala (c.134T>C) in the general population?

ACSM6 p.Val45Ala (c.134T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSM6 p.Val45Ala (c.134T>C)?

AlphaMissense predicts likely benign (score 0.0986) — an in-silico prediction, not a clinical call.

ACSM6 p.Val45Ala

c.134T>C · VCV4220329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0986	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.25	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 1.1	GERP 0.32, phastCons 0.003
Overall
CADD	14.75	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

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: ACSM6
Protein: p.Val45Ala
Coding: c.134T>C
MANE Select: NM_207321
Type: single nucleotide variant
Location: chr10:95194619 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.04

Full ACSM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM6 p.Ala20Gly Uncertain significance ★ ⚠ same type
ACSM6 p.Ala278Thr Uncertain significance ★ ⚠ same type
ACSM6 p.Ala441Thr Uncertain significance ★ ⚠ same type
ACSM6 p.Ala473Val Uncertain significance ★ ⚠ same type
ACSM6 p.Ala475Thr Uncertain significance ★ ⚠ same type
ACSM6 p.Ala73Pro Uncertain significance ★ ⚠ same type
ACSM6 p.Ala98Ser Uncertain significance ★ ⚠ same type
ACSM6 p.Arg113Gln 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/acsm6-p-val45ala (accessed [today's date]).

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