Is ACACA p.Arg2373Gln (c.7118G>A) pathogenic?

ACACA p.Arg2373Gln (c.7118G>A) is classified Uncertain significance in ACACA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-18). AlphaMissense: likely benign (0.0998); Very rare (popmax 0.00667%, amr).

How common is ACACA p.Arg2373Gln (c.7118G>A) in the general population?

ACACA p.Arg2373Gln (c.7118G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ACACA p.Arg2373Gln (c.7118G>A)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

ACACA p.Arg2373Gln

c.7118G>A · rs773877053 · VCV3001168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.23, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 101 kb · p 4.3e-52 · regional, not allelic
Overall
CADD	23.4	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 R2336Q vs ClinVar R2373Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,998 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00062% 10/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,999
Finnishnot grpmax-eligible	0.00156%	64,014
South Asian	0.0011%	91,072
European (non-Finnish)	0.000339%	295,005

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.Arg2373Gln
Coding: c.7118G>A
MANE Select: NM_198834
dbSNP: rs773877053
Type: single nucleotide variant
Location: chr17:37087350 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 10 PDB

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-arg2373gln (accessed [today's date]).

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