Is ACOT11 p.Ser388Arg (c.1164C>G) pathogenic?

ACOT11 p.Ser388Arg (c.1164C>G) is classified Uncertain significance in ACOT11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely pathogenic (0.9623); Absent from gnomAD v4.1.

How common is ACOT11 p.Ser388Arg (c.1164C>G) in the general population?

ACOT11 p.Ser388Arg (c.1164C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACOT11 p.Ser388Arg (c.1164C>G)?

AlphaMissense predicts likely pathogenic (score 0.9623) — an in-silico prediction, not a clinical call.

ACOT11 p.Ser388Arg

c.1164C>G · rs12038884 · VCV2479891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9623 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9623	likely pathogenic · top 6% in ACOT11
REVEL	0.728	pathogenic-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 61 kb · p 0.094 · regional, not allelic
Overall
CADD	25.3	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

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: ACOT11
Protein: p.Ser388Arg
Coding: c.1164C>G
MANE Select: NM_147161
dbSNP: rs12038884
Type: single nucleotide variant
Location: chr1:54604357 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.31 · 2 PDB
Residue 388: an α-helix; the start domain

Full ACOT11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOT11 p.Ala29Val Uncertain significance ★★ ⚠ same type
ACOT11 c.1629+9G>A Benign ★★ same type
ACOT11 c.884+6G>T Benign ★★ same type
ACOT11 p.Ile506= Benign ★★ same type
ACOT11 p.Val53= Benign ★★ same type
FAM151A p.Ala416Val Benign ★★ same type
FAM151A p.Arg534Gly Likely benign ★★ ⚠ same type
FAM151A p.Asp338= Benign ★★ 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/acot11-p-ser388arg (accessed [today's date]).

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