Is ACADS p.Trp177Arg (c.529T>C) pathogenic?

ACADS p.Trp177Arg (c.529T>C) is classified Pathogenic/Likely pathogenic in ACADS (ClinVar, Multiple submitters, 23 submitters; last evaluated 2026-03-05). AlphaMissense: likely pathogenic (0.9863); Rare (popmax 0.666%, afr); Associated with ACADS-related disorder.

What condition is associated with ACADS p.Trp177Arg (c.529T>C)?

ACADS p.Trp177Arg (c.529T>C) is associated with ACADS-related disorder, short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Trp177Arg (c.529T>C) in the general population?

ACADS p.Trp177Arg (c.529T>C) is rare (popmax 0.666%, afr) (gnomAD).

What do computational predictors say about ACADS p.Trp177Arg (c.529T>C)?

AlphaMissense predicts likely pathogenic (score 0.9863) — an in-silico prediction, not a clinical call.

ACADS p.Trp177Arg

c.529T>C · rs57443665 · VCV3828

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 23 submitters

AlphaMissense

likely pathogenic

0.9863 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.666%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACADS-related disorder

Computational evidence

Protein change
AlphaMissense	0.9863	likely pathogenic ✓ concordant with ClinVar · top 5% in ACADS
REVEL	0.957	strongly pathogenic-leaning
SaProt	LLR -12.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	27.8	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

Grpmax group 0.666% African / African-American · 500/75,036 alleles

Filtering AF 0.618% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.599%

Overall 0.0344% 555/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.666%	150
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Admixed American	0.0333%	3,001
Middle Eastern	0.0165%	6,060
South Asian	0.0011%	91,084
European (non-Finnish)	0.000339%	294,999

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: ACADS
Protein: p.Trp177Arg
Coding: c.529T>C
MANE Select: NM_000017
dbSNP: rs57443665
Type: single nucleotide variant
Location: chr12:120737893 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 177: a UniProt-annotated variant site (in acadsd); a β-strand

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

Disease context

ACADS-related disorder

Also linked: short chain acyl-CoA dehydrogenase deficiency

Similar variants

ACADS c.211-2A>G Likely pathogenic ★★ same condition
ACADS c.625-1G>A Likely pathogenic ★★ same condition
ACADS c.795+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Ala199Val Likely pathogenic ★★ ⚠ same condition
ACADS p.Arg107Cys Pathogenic ★★ ⚠ same condition
ACADS p.Arg272Cys Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg325Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ACADS p.Arg325Trp Pathogenic/Likely pathogenic ★★ same condition

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/acads-p-trp177arg (accessed [today's date]).

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