Is ACADM p.Ser38Arg (c.112A>C) pathogenic?

ACADM p.Ser38Arg (c.112A>C) is classified Uncertain significance in ACADM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-18). AlphaMissense: ambiguous (0.5301); Absent from gnomAD v4.1.

How common is ACADM p.Ser38Arg (c.112A>C) in the general population?

ACADM p.Ser38Arg (c.112A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADM p.Ser38Arg (c.112A>C)?

AlphaMissense predicts ambiguous (score 0.5301) — an in-silico prediction, not a clinical call.

ACADM p.Ser38Arg

c.112A>C · rs2100347323 · VCV1311433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5301	ambiguous
REVEL	0.581	indeterminate
SaProt	LLR -10.78	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 38 kb · p 0.63 · regional, not allelic
Overall
CADD	24.4	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: ACADM
Protein: p.Ser38Arg
Coding: c.112A>C
MANE Select: NM_000016
dbSNP: rs2100347323
Type: single nucleotide variant
Location: chr1:75728482 (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 38: a β-strand

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

Similar variants

ACADM p.Ser38delinsArgIleTer Pathogenic/Likely pathogenic ★★ 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
ACADM c.216+2T>C Pathogenic ★★ same type
ACADM c.216+2T>G 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-ser38arg (accessed [today's date]).

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