Is ACADL p.Ala117Pro (c.349G>C) pathogenic?

ACADL p.Ala117Pro (c.349G>C) is classified Uncertain significance in ACADL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: ambiguous (0.5324); Absent from gnomAD v4.1.

How common is ACADL p.Ala117Pro (c.349G>C) in the general population?

ACADL p.Ala117Pro (c.349G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACADL p.Ala117Pro (c.349G>C)?

AlphaMissense predicts ambiguous (score 0.5324) — an in-silico prediction, not a clinical call.

ACADL p.Ala117Pro

c.349G>C · VCV3996454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5324 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,986)

Computational evidence

Protein change
AlphaMissense	0.5324	ambiguous
REVEL	0.576	indeterminate
SaProt	LLR -10.55	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -3.5
Regional constraint	o/e 0.92	unconstrained · MANE · 36 kb · p 0.07 · regional, not allelic
Overall
CADD	10.82	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

No allele count reported in gnomAD v4.1 (AN 1,613,986). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACADL
Protein: p.Ala117Pro
Coding: c.349G>C
MANE Select: NM_001608
Type: single nucleotide variant
Location: chr2:210217987 (GRCh38)
Gene constraint: LOEUF 1.262 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.09 · 3 PDB
Residue 117: an α-helix

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

Similar variants

ACADL p.Glu308Lys Uncertain significance ★★ ⚠ same type
ACADL p.Ile170Val Uncertain significance ★★ ⚠ same type
ACADL p.Ala217= Likely benign ★★ same type
ACADL p.Lys333Gln Benign ★★ ⚠ same type
ACADL p.Tyr313= Likely benign ★★ same type
ACADL p.Val218= Benign ★★ same type
ACADL c.871-2A>G Uncertain significance ★ same type
ACADL p.Ala104Thr 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/acadl-p-ala117pro (accessed [today's date]).

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