Is KYNU p.Pro393= (c.1179G>A) pathogenic?

KYNU p.Pro393= (c.1179G>A) is classified Likely benign in KYNU (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). Very rare (popmax 0.00416%, nfe).

How common is KYNU p.Pro393= (c.1179G>A) in the general population?

KYNU p.Pro393= (c.1179G>A) is very rare (popmax 0.00416%, nfe) (gnomAD).

KYNU p.Pro393=

c.1179G>A · VCV4956842

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00416%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.64	GERP -2.2
Overall
CADD	5.612	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00416% European (non-Finnish) · 49/1,179,178 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00341% 55/1,612,694 alleles · very rare exomes 45/1,460,676 · genomes 10/152,018 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00641%	15,607
European (non-Finnish)grpmax	0.00416%	24,065
Finnishnot grpmax-eligible	0.00156%	63,996
African / African-American	0.00134%	74,850

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: KYNU
Protein: p.Pro393=
Coding: c.1179G>A
MANE Select: NM_003937
Type: single nucleotide variant
Location: chr2:143040565 (GRCh38)
Gene constraint: LOEUF 1.364 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.55 · 3 PDB
Residue 393: a UniProt-annotated variant site (in vcrl2; strongly reduced 3-hydroxykynureninase activity)

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

Similar variants

KYNU p.Pro393Leu Uncertain significance ★ ⚠ same residue
KYNU c.902+1G>A Pathogenic/Likely pathogenic ★★ same type
KYNU p.Arg428Trp Pathogenic/Likely pathogenic ★★ same type
KYNU p.Trp109Ser Pathogenic/Likely pathogenic ★★ same type
KYNU p.Tyr156Ter Pathogenic ★★ same type
KYNU p.Arg358Gln Uncertain significance ★★ ⚠ same type
KYNU p.Cys425Arg Uncertain significance ★★ ⚠ same type
KYNU p.Met187Arg 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/kynu-p-pro393 (accessed [today's date]).

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