Is ACOT4 p.Arg51Ser (c.151C>A) pathogenic?

ACOT4 p.Arg51Ser (c.151C>A) is classified Uncertain significance in ACOT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: ambiguous (0.3717); Very rare (popmax 0.00764%, sas).

How common is ACOT4 p.Arg51Ser (c.151C>A) in the general population?

ACOT4 p.Arg51Ser (c.151C>A) is very rare (popmax 0.00764%, sas) (gnomAD).

What do computational predictors say about ACOT4 p.Arg51Ser (c.151C>A)?

AlphaMissense predicts ambiguous (score 0.3717) — an in-silico prediction, not a clinical call.

ACOT4 p.Arg51Ser

c.151C>A · VCV3262004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3717 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00764%, sas)

Computational evidence

Protein change
AlphaMissense	0.3717	ambiguous
REVEL	0.396	indeterminate
SaProt	LLR -8.53	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 0.94, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 3,691 bp · p 0.48 · regional, not allelic
Overall
CADD	26.1	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 0.00764% South Asian · 6/78,520 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0022%

Overall 0.000397% 6/1,509,880 alleles · very rare

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: ACOT4
Protein: p.Arg51Ser
Coding: c.151C>A
MANE Select: NM_152331
Type: single nucleotide variant
Location: chr14:73592110 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.47 · 1 PDB
Residue 51: 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-arg51ser (accessed [today's date]).

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