Is ACAA1 p.Asp85= (c.255C>T) pathogenic?

ACAA1 p.Asp85= (c.255C>T) is classified Likely benign in ACAA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-28). Ultra-rare (popmax 0.0397%, nfe); Associated with ACAA1-related disorder.

What condition is associated with ACAA1 p.Asp85= (c.255C>T)?

ACAA1 p.Asp85= (c.255C>T) is associated with ACAA1-related disorder (ClinVar).

How common is ACAA1 p.Asp85= (c.255C>T) in the general population?

ACAA1 p.Asp85= (c.255C>T) is ultra-rare (popmax 0.0397%, nfe) (gnomAD).

ACAA1 p.Asp85=

c.255C>T · rs151286491 · VCV3057974

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0397%, nfe)

Conditions

ACAA1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.11	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2, phastCons 0.94
Overall
CADD	11.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0397% European (non-Finnish) · 469/1,180,008 alleles

Filtering AF 0.0367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0355%

Overall 0.0307% 495/1,613,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0397%	2,516
Remaining individualsnot grpmax-eligible	0.0336%	2,975
African / African-American	0.00667%	14,987

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: ACAA1
Protein: p.Asp85=
Coding: c.255C>T
MANE Select: NM_001607
dbSNP: rs151286491
Type: single nucleotide variant
Location: chr3:38136602 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 2 PDB

Full ACAA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACAA1-related disorder

Similar variants

ACAA1 c.546-4C>A Likely benign same condition
ACAA1 c.627-9T>C Likely benign same condition
ACAA1 p.Asp75Glu Likely benign same condition
ACAA1 p.Gln2= Likely benign same condition
ACAA1 p.Pro368= Likely benign same condition
ACAA1 p.Ser154= Benign same condition
ACAA1 p.Glu172Asp Benign ★★ same type
ACAA1 p.Ala131Ser 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/acaa1-p-asp85 (accessed [today's date]).

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