Is ACACB p.Asp2409Asn (c.7225G>A) pathogenic?

ACACB p.Asp2409Asn (c.7225G>A) is classified Likely benign in ACACB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-23). AlphaMissense: likely benign (0.1199); Rare (popmax 0.34%, afr); Associated with ACACB-related disorder.

What condition is associated with ACACB p.Asp2409Asn (c.7225G>A)?

ACACB p.Asp2409Asn (c.7225G>A) is associated with ACACB-related disorder (ClinVar).

How common is ACACB p.Asp2409Asn (c.7225G>A) in the general population?

ACACB p.Asp2409Asn (c.7225G>A) is rare (popmax 0.34%, afr) (gnomAD).

What do computational predictors say about ACACB p.Asp2409Asn (c.7225G>A)?

AlphaMissense predicts likely benign (score 0.1199) — an in-silico prediction, not a clinical call.

ACACB p.Asp2409Asn

c.7225G>A · VCV3352739

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1199 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.34%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ACACB-related disorder

Computational evidence

Protein change
AlphaMissense	0.1199	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 14 kb · p 5.4e-05 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 0.34% African / African-American · 255/75,034 alleles

Filtering AF 0.306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.292%

Overall 0.0456% 736/1,613,742 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.34%	294
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Admixed American	0.0433%	2,308
European (non-Finnish)	0.0354%	2,823
Middle Eastern	0.0331%	3,024
South Asian	0.00439%	22,766

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.Asp2409Asn
Coding: c.7225G>A
MANE Select: NM_001093
Type: single nucleotide variant
Location: chr12:109265500 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.29 · 11 PDB
Residue 2409: an α-helix

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

Disease context

ACACB-related disorder

Similar variants

ACACB p.Asp2409Glu Uncertain significance ★ ⚠ 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-asp2409asn (accessed [today's date]).

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