Is ACADS p.Ser111Phe (c.332C>T) pathogenic?

ACADS p.Ser111Phe (c.332C>T) is classified Uncertain significance in ACADS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-25). AlphaMissense: likely pathogenic (0.9837); Very rare (popmax 0.0024%, nfe); Associated with ACADS-related disorder.

What condition is associated with ACADS p.Ser111Phe (c.332C>T)?

ACADS p.Ser111Phe (c.332C>T) is associated with ACADS-related disorder, short chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADS p.Ser111Phe (c.332C>T) in the general population?

ACADS p.Ser111Phe (c.332C>T) is very rare (popmax 0.0024%, nfe) (gnomAD).

What do computational predictors say about ACADS p.Ser111Phe (c.332C>T)?

AlphaMissense predicts likely pathogenic (score 0.9837) — an in-silico prediction, not a clinical call.

ACADS p.Ser111Phe

c.332C>T · rs747339462 · VCV203552

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0024%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACADS-related disorder

Computational evidence

Protein change
AlphaMissense	0.9837	likely pathogenic · top 7% in ACADS
REVEL	0.955	strongly pathogenic-leaning
SaProt	LLR -15.55	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 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0024% European (non-Finnish) · 28/1,168,306 alleles

Filtering AF 0.00166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00189% 30/1,591,436 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0024%	41,725
Admixed American	0.00175%	57,168
Remaining individualsnot grpmax-eligible	0.00162%	61,544

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.Ser111Phe
Coding: c.332C>T
MANE Select: NM_000017
dbSNP: rs747339462
Type: single nucleotide variant
Location: chr12:120737107 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 111: an α-helix

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-ser111phe (accessed [today's date]).

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