Is ACADM p.Ala113Pro (c.337G>C) pathogenic?

ACADM p.Ala113Pro (c.337G>C) is classified Uncertain significance in ACADM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely pathogenic (0.9893); Very rare (popmax 8.47e-05%, nfe).

How common is ACADM p.Ala113Pro (c.337G>C) in the general population?

ACADM p.Ala113Pro (c.337G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ACADM p.Ala113Pro (c.337G>C)?

AlphaMissense predicts likely pathogenic (score 0.9893) — an in-silico prediction, not a clinical call.

ACADM p.Ala113Pro

c.337G>C · rs1570863351 · VCV806152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9893	likely pathogenic · top 6% in ACADM
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -14.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 38 kb · p 0.63 · regional, not allelic
Overall
CADD	28.2	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 8.47e-05% European (non-Finnish) · 1/1,180,018 alleles

Overall 6.84e-05% 1/1,461,828 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: ACADM
Protein: p.Ala113Pro
Coding: c.337G>C
MANE Select: NM_000016
dbSNP: rs1570863351
Type: single nucleotide variant
Location: chr1:75733578 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.15 · 7 PDB
Residue 113: an α-helix

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

Similar variants

ACADM p.Ala113Asp Pathogenic ★ same residue
ACADM p.Ala113Thr Likely pathogenic ★ same residue
ACADM p.Ala113= Uncertain significance same residue
ACADM c.118+1G>T Likely pathogenic ★★ same type
ACADM c.1194+1G>A Pathogenic/Likely pathogenic ★★ same type
ACADM c.1194+2T>G Likely pathogenic ★★ same type
ACADM c.216+1G>A Pathogenic ★★ same type
ACADM c.216+1G>T Pathogenic/Likely pathogenic ★★ 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/acadm-p-ala113pro (accessed [today's date]).

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