Is ACACA p.Val1283Ile (c.3847G>A) pathogenic?

ACACA p.Val1283Ile (c.3847G>A) is classified Uncertain significance in ACACA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.0871); Rare (popmax 0.138%, eas).

How common is ACACA p.Val1283Ile (c.3847G>A) in the general population?

ACACA p.Val1283Ile (c.3847G>A) is rare (popmax 0.138%, eas) (gnomAD).

What do computational predictors say about ACACA p.Val1283Ile (c.3847G>A)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

ACACA p.Val1283Ile

c.3847G>A · rs368681413 · VCV3133480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 18 kb · p 6e-10 · regional, not allelic
Overall
CADD	19.67	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 V1246I vs ClinVar V1283I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% East Asian · 62/44,882 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00539% 87/1,613,920 alleles · rare exomes 75/1,461,642 · genomes 12/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.138%	724
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.00333%	29,993
South Asian	0.00329%	30,359
African / African-American	0.00133%	75,028
European (non-Finnish)	8.48e-05%	1,179,876

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.Val1283Ile
Coding: c.3847G>A
MANE Select: NM_198834
dbSNP: rs368681413
Type: single nucleotide variant
Location: chr17:37207661 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.05 · 10 PDB
Residue 1246 UniProt numbering: an α-helix

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

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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-val1283ile (accessed [today's date]).

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