Is ACOT9 p.Pro204Ser (c.610C>T) pathogenic?

ACOT9 p.Pro204Ser (c.610C>T) is classified Uncertain significance in ACOT9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.1058); Very rare (popmax 0.00177%, sas).

How common is ACOT9 p.Pro204Ser (c.610C>T) in the general population?

ACOT9 p.Pro204Ser (c.610C>T) is very rare (popmax 0.00177%, sas) (gnomAD).

What do computational predictors say about ACOT9 p.Pro204Ser (c.610C>T)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

ACOT9 p.Pro204Ser

c.610C>T · rs1928959433 · VCV2271333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 9.6	GERP 4.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 39 kb · p 0.094 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P195S vs ClinVar P204S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00177% South Asian · 1/56,458 alleles

Overall 0.000183% 2/1,092,585 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00211%	47,448
South Asiangrpmax	0.00177%	56,458

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACOT9
Protein: p.Pro204Ser
Coding: c.610C>T
MANE Select: NM_001037171
dbSNP: rs1928959433
Type: single nucleotide variant
Location: chrX:23713187 (GRCh38)
Structure: AlphaFold pLDDT 85.31
Residue 204: the hotdog acot-type 1 domain

Full ACOT9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOT9 p.Ala438Val Likely benign ★★ same type
ACOT9 p.His198Arg Likely benign ★★ same type
ACOT9 p.Ala146Pro Uncertain significance ★ ⚠ same type
ACOT9 p.Arg110Gln Uncertain significance ★ ⚠ same type
ACOT9 p.Arg215Cys Uncertain significance ★ ⚠ same type
ACOT9 p.Arg286Trp Uncertain significance ★ ⚠ same type
ACOT9 p.Arg313Trp Uncertain significance ★ ⚠ same type
ACOT9 p.Arg343Pro 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/acot9-p-pro204ser (accessed [today's date]).

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