Is ACACA p.Arg183= (c.547C>A) pathogenic?

ACACA p.Arg183= (c.547C>A) is classified Benign/Likely benign in ACACA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Rare (popmax 0.569%, nfe).

How common is ACACA p.Arg183= (c.547C>A) in the general population?

ACACA p.Arg183= (c.547C>A) is rare (popmax 0.569%, nfe) (gnomAD).

ACACA p.Arg183=

c.547C>A · rs111441513 · VCV559350

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.569%, nfe)

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 3.8	GERP 0.08, phastCons 1
Overall
CADD	10.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.569% European (non-Finnish) · 6,717/1,179,988 alleles

Filtering AF 0.558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.553%

Overall 0.471% 7,606/1,614,038 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.595%	168
European (non-Finnish)grpmax	0.569%	176
Finnishnot grpmax-eligible	0.436%	229
Remaining individualsnot grpmax-eligible	0.357%	280
Admixed American	0.265%	377
African / African-American	0.0667%	1,500
Middle Eastern	0.0165%	6,062
South Asian	0.0011%	91,074

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACACA
Protein: p.Arg183=
Coding: c.547C>A
MANE Select: NM_198834
dbSNP: rs111441513
Type: single nucleotide variant
Location: chr17:37283330 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 10 PDB
Residue 183: the biotin carboxylation domain; an α-helix

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

Similar variants

ACACA p.Ala2308Val Uncertain significance ★★ ⚠ same type
ACACA p.Arg1206His Uncertain significance ★★ ⚠ same type
ACACA p.Arg2198Gln Uncertain significance ★★ ⚠ same type
ACACA p.Arg745Trp Uncertain significance ★★ ⚠ same type
ACACA p.Asn1903Ser Uncertain significance ★★ ⚠ same type
ACACA p.Asn728Ser Uncertain significance ★★ ⚠ same type
ACACA p.Asn950Ser Uncertain significance ★★ ⚠ same type
ACACA p.Asp2228Asn 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/acaca-p-arg183 (accessed [today's date]).

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