Is ACER3 p.Ala65Pro (c.193G>C) pathogenic?

ACER3 p.Ala65Pro (c.193G>C) is classified Uncertain significance in ACER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely pathogenic (0.8978); Absent from gnomAD v4.1; Associated with neuromuscular disease.

What condition is associated with ACER3 p.Ala65Pro (c.193G>C)?

ACER3 p.Ala65Pro (c.193G>C) is associated with neuromuscular disease (ClinVar).

How common is ACER3 p.Ala65Pro (c.193G>C) in the general population?

ACER3 p.Ala65Pro (c.193G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACER3 p.Ala65Pro (c.193G>C)?

AlphaMissense predicts likely pathogenic (score 0.8978) — an in-silico prediction, not a clinical call.

ACER3 p.Ala65Pro

c.193G>C · VCV3383277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuromuscular disease

Computational evidence

Protein change
AlphaMissense	0.8978	likely pathogenic
REVEL	0.202	benign-leaning
SaProt	LLR -14.65	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 159 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	24.2	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: ACER3
Protein: p.Ala65Pro
Coding: c.193G>C
MANE Select: NM_018367
Type: single nucleotide variant
Location: chr11:76926646 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 93.23 · 2 PDB
Residue 65: an α-helix

Full ACER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuromuscular disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACER3 c.751-5A>G Uncertain significance ★ same condition
ACER3 p.Ala2Pro Uncertain significance ★★ ⚠ same type
ACER3 p.Ala4Thr Uncertain significance ★★ ⚠ same type
ACER3 p.Arg62Gln Uncertain significance ★★ ⚠ same type
ACER3 p.Gly12Asp Uncertain significance ★★ ⚠ same type
ACER3 p.Ile97Leu Uncertain significance ★★ ⚠ same type
ACER3 p.Val206Ile Uncertain significance ★★ ⚠ same type
ACER3 c.214+19C>G Benign ★★ 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/acer3-p-ala65pro (accessed [today's date]).

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