Is ACOT7 p.Asn86Ser (c.257A>G) pathogenic?

ACOT7 p.Asn86Ser (c.257A>G) is classified Uncertain significance in ACOT7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0798); Absent from gnomAD v4.1.

How common is ACOT7 p.Asn86Ser (c.257A>G) in the general population?

ACOT7 p.Asn86Ser (c.257A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACOT7 p.Asn86Ser (c.257A>G)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

ACOT7 p.Asn86Ser

c.257A>G · VCV3999156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -4.47	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 0.86	GERP -1.4, phastCons 0.73
Regional constraint	o/e 0.66	unconstrained · MANE · 129 kb · p 1e-13 · regional, not allelic
Overall
CADD	13.75	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 N96S vs ClinVar N86S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACOT7
Protein: p.Asn86Ser
Coding: c.257A>G
MANE Select: NM_007274
Type: single nucleotide variant
Location: chr1:6349753 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 86: 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-asn86ser (accessed [today's date]).

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