Is ACSM6 p.Ser95Tyr (c.284C>A) pathogenic?

ACSM6 p.Ser95Tyr (c.284C>A) is classified Uncertain significance in ACSM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.8109); Very rare (popmax 0.00061%, nfe).

How common is ACSM6 p.Ser95Tyr (c.284C>A) in the general population?

ACSM6 p.Ser95Tyr (c.284C>A) is very rare (popmax 0.00061%, nfe) (gnomAD).

What do computational predictors say about ACSM6 p.Ser95Tyr (c.284C>A)?

AlphaMissense predicts likely pathogenic (score 0.8109) — an in-silico prediction, not a clinical call.

ACSM6 p.Ser95Tyr

c.284C>A · VCV4220305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00061%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8109	likely pathogenic · top 2% in ACSM6
REVEL	0.201	benign-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP 0.83
Overall
CADD	18.49	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

Grpmax group 0.00061% European (non-Finnish) · 7/1,147,060 alleles

Filtering AF 0.000254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000451% 7/1,551,858 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: ACSM6
Protein: p.Ser95Tyr
Coding: c.284C>A
MANE Select: NM_207321
Type: single nucleotide variant
Location: chr10:95202076 (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-ser95tyr (accessed [today's date]).

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