Is ACADL p.Met367Val (c.1099A>G) pathogenic?

ACADL p.Met367Val (c.1099A>G) is classified Uncertain significance in ACADL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.2399); Very rare (popmax 0.004%, afr).

How common is ACADL p.Met367Val (c.1099A>G) in the general population?

ACADL p.Met367Val (c.1099A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ACADL p.Met367Val (c.1099A>G)?

AlphaMissense predicts likely benign (score 0.2399) — an in-silico prediction, not a clinical call.

ACADL p.Met367Val

c.1099A>G · rs1391387036 · VCV2242033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2399 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2399	likely benign
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -8.88	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 4.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 36 kb · p 0.07 · regional, not allelic
Overall
CADD	25.1	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

Grpmax group 0.004% African / African-American · 3/74,918 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,824 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
European (non-Finnish)	8.48e-05%	1,179,915

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: ACADL
Protein: p.Met367Val
Coding: c.1099A>G
MANE Select: NM_001608
dbSNP: rs1391387036
Type: single nucleotide variant
Location: chr2:210195224 (GRCh38)
Gene constraint: LOEUF 1.262 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.09 · 3 PDB
Residue 367: 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-met367val (accessed [today's date]).

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