Is KCTD7 p.Ser91= (c.273C>T) pathogenic?

KCTD7 p.Ser91= (c.273C>T) is classified Conflicting classifications of pathogenicity in KCTD7 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.099%, mid); Associated with Inborn genetic diseases.

What condition is associated with KCTD7 p.Ser91= (c.273C>T)?

KCTD7 p.Ser91= (c.273C>T) is associated with Inborn genetic diseases, progressive myoclonic epilepsy type 3 (ClinVar).

How common is KCTD7 p.Ser91= (c.273C>T) in the general population?

KCTD7 p.Ser91= (c.273C>T) is ultra-rare (popmax 0.099%, mid) (gnomAD).

KCTD7 p.Ser91=

c.273C>T · rs139585796 · VCV206008

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Conditions

Inborn genetic diseases

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 -20
Overall
CADD	1.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,060 alleles

Filtering AF 0.0619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0555%

Overall 0.0377% 609/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
Admixed American	0.08%	1,250
Remaining individualsnot grpmax-eligible	0.0432%	2,315
European (non-Finnish)	0.0426%	2,346
South Asian	0.0165%	6,071
African / African-American	0.0107%	9,372
East Asian	0.00223%	44,862
Finnishnot grpmax-eligible	0.00156%	64,018

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: KCTD7
Protein: p.Ser91=
Coding: c.273C>T
MANE Select: NM_153033
dbSNP: rs139585796
Type: single nucleotide variant
Location: chr7:66633403 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67
Residue 91: the btb domain

Full KCTD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: progressive myoclonic epilepsy type 3

Similar variants

KCTD7 c.145-2A>G Likely pathogenic ★★ same condition
KCTD7 p.Ala174Thr Likely pathogenic ★★ ⚠ same condition
KCTD7 p.Arg184Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
KCTD7 p.Arg211Ter Pathogenic/Likely pathogenic ★★ same condition
KCTD7 p.Arg99Ter Pathogenic ★★ same condition
KCTD7 p.Tyr276Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
KCTD7 c.144+3A>G Uncertain significance ★★ same condition
KCTD7 p.Ala124Gly Uncertain significance ★★ ⚠ same condition

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/kctd7-p-ser91 (accessed [today's date]).

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