Is ACACA p.Gly1272Arg (c.3814G>A) pathogenic?

ACACA p.Gly1272Arg (c.3814G>A) is classified Uncertain significance in ACACA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely pathogenic (0.9826); Ultra-rare (popmax 0.056%, sas).

How common is ACACA p.Gly1272Arg (c.3814G>A) in the general population?

ACACA p.Gly1272Arg (c.3814G>A) is ultra-rare (popmax 0.056%, sas) (gnomAD).

What do computational predictors say about ACACA p.Gly1272Arg (c.3814G>A)?

AlphaMissense predicts likely pathogenic (score 0.9826) — an in-silico prediction, not a clinical call.

ACACA p.Gly1272Arg

c.3814G>A · VCV3804403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9826 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9826	likely pathogenic
REVEL	0.281	benign-leaning
SaProt	LLR -3.50	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 18 kb · p 6e-10 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G1235R vs ClinVar G1272R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% South Asian · 51/91,070 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00378% 61/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Remaining individualsnot grpmax-eligible	0.0112%	8,929
East Asian	0.00223%	44,880
Admixed American	0.00167%	60,014
African / African-American	0.00133%	75,040

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.Gly1272Arg
Coding: c.3814G>A
MANE Select: NM_198834
Type: single nucleotide variant
Location: chr17:37207694 (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

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ACACA p.Asn728Ser Uncertain significance ★★ ⚠ same type
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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-gly1272arg (accessed [today's date]).

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