Is ACOT9 p.Ala438Val (c.1313C>T) pathogenic?

ACOT9 p.Ala438Val (c.1313C>T) is classified Likely benign in ACOT9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-01). AlphaMissense: likely benign (0.0636); Ultra-rare (popmax 0.0108%, nfe).

How common is ACOT9 p.Ala438Val (c.1313C>T) in the general population?

ACOT9 p.Ala438Val (c.1313C>T) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

What do computational predictors say about ACOT9 p.Ala438Val (c.1313C>T)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

ACOT9 p.Ala438Val

c.1313C>T · rs200042097 · VCV2365521

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.88	GERP -4.2
Regional constraint	o/e 0.91	unconstrained · MANE · 39 kb · p 0.094 · regional, not allelic
Overall
CADD	0.007	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 A429V vs ClinVar A438V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% European (non-Finnish) · 97/894,567 alleles

Filtering AF 0.00909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00835%

Overall 0.0258% 312/1,208,692 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.881%	113
Remaining individualsnot grpmax-eligible	0.0399%	2,503
European (non-Finnish)grpmax	0.0108%	9,222
East Asian	0.00296%	33,738
African / African-American	0.00175%	57,001

Ashkenazi Jewish 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.Ala438Val
Coding: c.1313C>T
MANE Select: NM_001037171
dbSNP: rs200042097
Type: single nucleotide variant
Location: chrX:23703928 (GRCh38)
Structure: AlphaFold pLDDT 85.31

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

Similar variants

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
ACOT9 p.Arg429Trp 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-ala438val (accessed [today's date]).

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