Is ACOT7 p.Asp266= (c.798C>T) pathogenic?

ACOT7 p.Asp266= (c.798C>T) is classified Benign in ACOT7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). Common (popmax 8.66%, afr) — too common for a highly-penetrant pathogenic allele.

ACOT7 p.Asp266=

Q: How common is ACOT7 p.Asp266= (c.798C>T) in the general population?

ACOT7 p.Asp266= (c.798C>T) is common (popmax 8.66%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.798C>T · rs1804843 · VCV775495

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.66%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.5	GERP -5.3
Overall
CADD	0.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.66% African / African-American · 6,498/74,994 alleles

Filtering AF 8.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.42%

Overall 0.459% 7,409/1,613,984 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.66%	12
Remaining individualsnot grpmax-eligible	0.544%	184
Ashkenazi Jewishnot grpmax-eligible	0.513%	195
Admixed American	0.468%	214
Middle Eastern	0.215%	466
South Asian	0.0121%	8,280
European (non-Finnish)	0.00949%	10,536
East Asian	0.00446%	22,440

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: ACOT7
Protein: p.Asp266=
Coding: c.798C>T
MANE Select: NM_007274
dbSNP: rs1804843
Type: single nucleotide variant
Location: chr1:6294895 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 266: the hotdog acot-type 2 domain; an α-helix

Full ACOT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOT7 c.143+7600C>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7603G>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7604C>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7615C>G Uncertain significance ★ ⚠ same type
ACOT7 c.143+7615C>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7660G>A Uncertain significance ★ same type
ACOT7 c.143+7684C>T Uncertain significance ★ ⚠ same type
ACOT7 c.143+7685G>A 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/acot7-p-asp266 (accessed [today's date]).

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