Is PIGQ p.Phe397= (c.1191C>T) pathogenic?

PIGQ p.Phe397= (c.1191C>T) is classified Likely benign in PIGQ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-04). Very rare (popmax 0.00267%, afr); Associated with epilepsy.

What condition is associated with PIGQ p.Phe397= (c.1191C>T)?

PIGQ p.Phe397= (c.1191C>T) is associated with epilepsy (ClinVar).

How common is PIGQ p.Phe397= (c.1191C>T) in the general population?

PIGQ p.Phe397= (c.1191C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

PIGQ p.Phe397=

c.1191C>T · rs370675673 · VCV1146081

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

epilepsy

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 2.2	GERP 0.3, phastCons 1
Overall
CADD	13.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,320 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,457
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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: PIGQ
Protein: p.Phe397=
Coding: c.1191C>T
MANE Select: NM_004204
dbSNP: rs370675673
Type: single nucleotide variant
Location: chr16:578906 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.70
Residue 397: a UniProt-annotated variant site (in mcahs4)

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

Disease context

epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGQ c.942+1G>A Pathogenic/Likely pathogenic ★★ same condition
PIGQ c.942+1G>C Pathogenic ★★ same condition
PIGQ p.Gln140Ter Pathogenic/Likely pathogenic ★★ same condition
PIGQ p.Gln271Ter Pathogenic/Likely pathogenic ★★ same condition
PIGQ c.690-3C>A Uncertain significance ★★ same condition
PIGQ p.Ala163Gly Uncertain significance ★★ ⚠ same condition
PIGQ p.Ala202Thr Uncertain significance ★★ ⚠ same condition
PIGQ p.Ala205Ser 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/pigq-p-phe397 (accessed [today's date]).

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