Is ACSM5 p.Ser310Pro (c.928T>C) pathogenic?

ACSM5 p.Ser310Pro (c.928T>C) is classified Uncertain significance in ACSM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: ambiguous (0.4502); Absent from gnomAD v4.1.

How common is ACSM5 p.Ser310Pro (c.928T>C) in the general population?

ACSM5 p.Ser310Pro (c.928T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACSM5 p.Ser310Pro (c.928T>C)?

AlphaMissense predicts ambiguous (score 0.4502) — an in-silico prediction, not a clinical call.

ACSM5 p.Ser310Pro

c.928T>C · VCV3825540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4502 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4502	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -14.84	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.77	GERP -3.5
Regional constraint	o/e 1.00	unconstrained · MANE · 29 kb · p 0.91 · regional, not allelic
Overall
CADD	18.7	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: ACSM5
Protein: p.Ser310Pro
Coding: c.928T>C
MANE Select: NM_017888
Type: single nucleotide variant
Location: chr16:20427794 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.58

Full ACSM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM5 p.Pro144Leu Uncertain significance ★★ ⚠ same type
ACSM5 c.1001+10G>A Benign ★★ same type
ACSM5 p.His360Arg Benign ★★ same type
ACSM5 p.Ala160Val Uncertain significance ★ ⚠ same type
ACSM5 p.Ala163Ser Uncertain significance ★ ⚠ same type
ACSM5 p.Arg100Ser Uncertain significance ★ ⚠ same type
ACSM5 p.Arg157Trp Uncertain significance ★ ⚠ same type
ACSM5 p.Arg197Trp 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/acsm5-p-ser310pro (accessed [today's date]).

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