Is ACOT7 p.Arg80Gln (c.239G>A) pathogenic?

ACOT7 p.Arg80Gln (c.239G>A) is classified Uncertain significance in ACOT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely pathogenic (0.75); Very rare (popmax 0.000339%, nfe).

How common is ACOT7 p.Arg80Gln (c.239G>A) in the general population?

ACOT7 p.Arg80Gln (c.239G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ACOT7 p.Arg80Gln (c.239G>A)?

AlphaMissense predicts likely pathogenic (score 0.75) — an in-silico prediction, not a clinical call.

ACOT7 p.Arg80Gln

c.239G>A · VCV3481729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.75 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.75	likely pathogenic
REVEL	0.209	benign-leaning
SaProt	LLR -13.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 129 kb · p 1e-13 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R90Q vs ClinVar R80Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,934 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000411% 6/1,461,552 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
European (non-Finnish)grpmax	0.000339%	294,984

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg80Gln
Coding: c.239G>A
MANE Select: NM_007274
Type: single nucleotide variant
Location: chr1:6349771 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 80: the hotdog acot-type 1 domain

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

Similar variants

ACOT7 p.Arg80Trp Uncertain significance ★ ⚠ 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
ACOT7 c.143+7660G>A 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-arg80gln (accessed [today's date]).

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