Is ACAA1 p.Ile48Phe (c.142A>T) pathogenic?

ACAA1 p.Ile48Phe (c.142A>T) is classified Uncertain significance in ACAA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.4362); Absent from gnomAD v4.1.

How common is ACAA1 p.Ile48Phe (c.142A>T) in the general population?

ACAA1 p.Ile48Phe (c.142A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAA1 p.Ile48Phe (c.142A>T)?

AlphaMissense predicts ambiguous (score 0.4362) — an in-silico prediction, not a clinical call.

ACAA1 p.Ile48Phe

c.142A>T · VCV4195935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4362 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4362	ambiguous
REVEL	0.748	pathogenic-leaning
SaProt	LLR -7.95	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.034 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACAA1
Protein: p.Ile48Phe
Coding: c.142A>T
MANE Select: NM_001607
Type: single nucleotide variant
Location: chr3:38136894 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.93 · 2 PDB

Full ACAA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAA1 p.Glu172Asp Benign ★★ same type
ACAA1 p.Ala131Ser Uncertain significance ★ ⚠ same type
ACAA1 p.Ala24Val Uncertain significance ★ ⚠ same type
ACAA1 p.Ala324Gly Uncertain significance ★ ⚠ same type
ACAA1 p.Ala33Thr Uncertain significance ★ ⚠ same type
ACAA1 p.Ala416Thr Uncertain significance ★ ⚠ same type
ACAA1 p.Arg167Cys Uncertain significance ★ ⚠ same type
ACAA1 p.Arg167His 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/acaa1-p-ile48phe (accessed [today's date]).

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