Is ACAA1 p.Gly235Val (c.704G>T) pathogenic?

ACAA1 p.Gly235Val (c.704G>T) is classified Uncertain significance in ACAA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: ambiguous (0.3936); Ultra-rare (popmax 0.0266%, afr).

How common is ACAA1 p.Gly235Val (c.704G>T) in the general population?

ACAA1 p.Gly235Val (c.704G>T) is ultra-rare (popmax 0.0266%, afr) (gnomAD).

What do computational predictors say about ACAA1 p.Gly235Val (c.704G>T)?

AlphaMissense predicts ambiguous (score 0.3936) — an in-silico prediction, not a clinical call.

ACAA1 p.Gly235Val

c.704G>T · VCV4195506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0266%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3936	ambiguous
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -15.75	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.034 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.0266% African / African-American · 20/75,050 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00161% 26/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0266%	3,753
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)	8.47e-05%	1,180,002

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: ACAA1
Protein: p.Gly235Val
Coding: c.704G>T
MANE Select: NM_001607
Type: single nucleotide variant
Location: chr3:38126623 (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-gly235val (accessed [today's date]).

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