Is ACACA p.Asn309Ser (c.926A>G) pathogenic?

ACACA p.Asn309Ser (c.926A>G) is classified Uncertain significance in ACACA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-02-15). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.00864%, nfe).

How common is ACACA p.Asn309Ser (c.926A>G) in the general population?

ACACA p.Asn309Ser (c.926A>G) is very rare (popmax 0.00864%, nfe) (gnomAD).

What do computational predictors say about ACACA p.Asn309Ser (c.926A>G)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

ACACA p.Asn309Ser

c.926A>G · rs760250740 · VCV559349

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00864%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -5.60	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 0.87	GERP 0.86, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,780 bp · p 0.26 · regional, not allelic
Overall
CADD	17.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N272S vs ClinVar N309S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00864% European (non-Finnish) · 102/1,179,996 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00657% 106/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00864%	11,569
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00267%	37,461

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.Asn309Ser
Coding: c.926A>G
MANE Select: NM_198834
dbSNP: rs760250740
Type: single nucleotide variant
Location: chr17:37274275 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 10 PDB
Residue 309: the biotin carboxylation domain; a β-strand; the atp-grasp domain

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-asn309ser (accessed [today's date]).

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