Is ACACB p.Pro43= (c.129G>A) pathogenic?

ACACB p.Pro43= (c.129G>A) is classified Likely benign in ACACB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-14). Ultra-rare (popmax 0.0111%, eas); Associated with ACACB-related disorder.

What condition is associated with ACACB p.Pro43= (c.129G>A)?

ACACB p.Pro43= (c.129G>A) is associated with ACACB-related disorder (ClinVar).

How common is ACACB p.Pro43= (c.129G>A) in the general population?

ACACB p.Pro43= (c.129G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

ACACB p.Pro43=

c.129G>A · rs146888683 · VCV3038985

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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 -4.1
Overall
CADD	0.965	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,890 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00211% 34/1,613,832 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
South Asian	0.00549%	18,210
Admixed American	0.005%	19,989
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00161%	62,106

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: ACACB
Protein: p.Pro43=
Coding: c.129G>A
MANE Select: NM_001093
dbSNP: rs146888683
Type: single nucleotide variant
Location: chr12:109139534 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.29 · 11 PDB
Residue 43: the 'disordered' region

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

Disease context

ACACB-related disorder

Similar variants

ACACB p.Pro43Leu Likely benign ★ same residue
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

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-pro43 (accessed [today's date]).

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