Is ACOT7 p.Ala366Val (c.1097C>T) pathogenic?

ACOT7 p.Ala366Val (c.1097C>T) is classified Uncertain significance in ACOT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0647); Rare (popmax 0.103%, afr).

How common is ACOT7 p.Ala366Val (c.1097C>T) in the general population?

ACOT7 p.Ala366Val (c.1097C>T) is rare (popmax 0.103%, afr) (gnomAD).

What do computational predictors say about ACOT7 p.Ala366Val (c.1097C>T)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

ACOT7 p.Ala366Val

c.1097C>T · rs139667005 · VCV3137933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.9
Regional constraint	o/e 0.66	unconstrained · MANE · 129 kb · p 1e-13 · regional, not allelic
Overall
CADD	5.667	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A376V vs ClinVar A366V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% African / African-American · 77/75,048 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0773%

Overall 0.00763% 123/1,612,674 alleles · rare exomes 71/1,460,316 · genomes 52/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	975
Admixed American	0.00834%	11,996
South Asian	0.00549%	18,200
European (non-Finnish)	0.00297%	33,709
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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: ACOT7
Protein: p.Ala366Val
Coding: c.1097C>T
MANE Select: NM_007274
dbSNP: rs139667005
Type: single nucleotide variant
Location: chr1:6264613 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 376 UniProt numbering: the 'disordered' region

Full ACOT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOT7 p.Ala366Ser Uncertain significance ★ ⚠ same residue
ACOT7 p.Ala366Thr Likely benign ★ same residue
ACOT7 p.Asp266= Benign ★★ same type
ACOT7 c.143+7600C>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7603G>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7604C>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7615C>G Uncertain significance ★ ⚠ same type
ACOT7 c.143+7615C>T 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/acot7-p-ala366val (accessed [today's date]).

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