Is ACOT7 p.Arg89Cys (c.265C>T) pathogenic?

ACOT7 p.Arg89Cys (c.265C>T) is classified Uncertain significance in ACOT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.1637); Ultra-rare (popmax 0.0245%, eas).

How common is ACOT7 p.Arg89Cys (c.265C>T) in the general population?

ACOT7 p.Arg89Cys (c.265C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about ACOT7 p.Arg89Cys (c.265C>T)?

AlphaMissense predicts likely benign (score 0.1637) — an in-silico prediction, not a clinical call.

ACOT7 p.Arg89Cys

c.265C>T · VCV3262056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1637 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1637	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -9.79	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 5.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 129 kb · p 1e-13 · regional, not allelic
Overall
CADD	27.0	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 R99C vs ClinVar R89C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,872 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00143% 23/1,612,578 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,079
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.000933%	107,223

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.Arg89Cys
Coding: c.265C>T
MANE Select: NM_007274
Type: single nucleotide variant
Location: chr1:6339586 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 89: the hotdog acot-type 1 domain

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

Similar variants

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
ACOT7 c.143+7684C>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-arg89cys (accessed [today's date]).

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