Is ACACB p.His2301= (c.6903T>C) pathogenic?

ACACB p.His2301= (c.6903T>C) is classified Likely benign in ACACB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD v4.1; Associated with ACACB-related disorder.

What condition is associated with ACACB p.His2301= (c.6903T>C)?

ACACB p.His2301= (c.6903T>C) is associated with ACACB-related disorder (ClinVar).

How common is ACACB p.His2301= (c.6903T>C) in the general population?

ACACB p.His2301= (c.6903T>C) is absent from gnomAD v4.1 (gnomAD).

ACACB p.His2301=

c.6903T>C · rs2136864870 · VCV3039357

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ACACB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP 0.057
Overall
CADD	1.234	PHRED · no single calibrated threshold — expert panels disagree

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: ACACB
Protein: p.His2301=
Coding: c.6903T>C
MANE Select: NM_001093
dbSNP: rs2136864870
Type: single nucleotide variant
Location: chr12:109264347 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.29 · 11 PDB
Residue 2301: an α-helix; the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region

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

Disease context

ACACB-related disorder

Similar variants

ACACB p.Arg939Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
ACACB p.Phe578Leu Uncertain significance ★ ⚠ same condition
ACACB p.Ser1199= Conflicting classifications of pathogenicity ★ same condition
ACACB p.Glu1608Lys Uncertain significance ⚠ same condition
ACACB p.Met1253Thr Uncertain significance ⚠ same condition
ACACB p.Met2164Thr Uncertain significance ⚠ same condition
ACACB c.1117+3A>G Likely benign same condition
ACACB c.1819-7A>G Likely benign same condition

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/acacb-p-his2301 (accessed [today's date]).

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