Is ACADM p.Leu313Pro (c.938T>C) pathogenic?

ACADM p.Leu313Pro (c.938T>C) is classified Uncertain significance in ACADM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-27). AlphaMissense: likely pathogenic (0.8451); Absent from gnomAD v4.1.

How common is ACADM p.Leu313Pro (c.938T>C) in the general population?

ACADM p.Leu313Pro (c.938T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADM p.Leu313Pro (c.938T>C)?

AlphaMissense predicts likely pathogenic (score 0.8451) — an in-silico prediction, not a clinical call.

ACADM p.Leu313Pro

c.938T>C · rs886042085 · VCV281047

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8451 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8451	likely pathogenic
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -12.62	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 38 kb · p 0.63 · regional, not allelic
Overall
CADD	24.5	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

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.Leu313Pro
Coding: c.938T>C
MANE Select: NM_000016
dbSNP: rs886042085
Type: single nucleotide variant
Location: chr1:75750539 (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 313: an α-helix

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

Similar variants

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
ACADM c.217-1G>A 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-leu313pro (accessed [today's date]).

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