Is ACOT4 p.Phe102Ser (c.305T>C) pathogenic?

ACOT4 p.Phe102Ser (c.305T>C) is classified Uncertain significance in ACOT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.332); Absent from gnomAD v4.1.

How common is ACOT4 p.Phe102Ser (c.305T>C) in the general population?

ACOT4 p.Phe102Ser (c.305T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACOT4 p.Phe102Ser (c.305T>C)?

AlphaMissense predicts likely benign (score 0.332) — an in-silico prediction, not a clinical call.

ACOT4 p.Phe102Ser

c.305T>C · VCV4216827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.332 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,170)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.332	likely benign
REVEL	0.336	indeterminate
SaProt	LLR -11.34	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.88, phastCons 0.011
Regional constraint	o/e 1.03	unconstrained · MANE · 3,691 bp · p 0.48 · regional, not allelic
Overall
CADD	22.5	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

No allele count reported in gnomAD v4.1 (AN 1,613,170). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACOT4
Protein: p.Phe102Ser
Coding: c.305T>C
MANE Select: NM_152331
Type: single nucleotide variant
Location: chr14:73592264 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.47 · 1 PDB
Residue 102: a β-strand

Full ACOT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOT4 p.Ala235Gly Uncertain significance ★ ⚠ same type
ACOT4 p.Ala235Thr Uncertain significance ★ ⚠ same type
ACOT4 p.Ala242Ser Uncertain significance ★ ⚠ same type
ACOT4 p.Ala242Val Uncertain significance ★ ⚠ same type
ACOT4 p.Ala372Gly Uncertain significance ★ ⚠ same type
ACOT4 p.Ala48Thr Uncertain significance ★ ⚠ same type
ACOT4 p.Ala65Thr Uncertain significance ★ ⚠ same type
ACOT4 p.Ala65Val 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/acot4-p-phe102ser (accessed [today's date]).

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