Is KY p.Ala591= (c.1773C>T) pathogenic?

KY p.Ala591= (c.1773C>T) is classified Likely benign in KY (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-31). Very rare (popmax 0.0044%, sas); Associated with KY-related disorder.

What condition is associated with KY p.Ala591= (c.1773C>T)?

KY p.Ala591= (c.1773C>T) is associated with KY-related disorder (ClinVar).

How common is KY p.Ala591= (c.1773C>T) in the general population?

KY p.Ala591= (c.1773C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

KY p.Ala591=

c.1773C>T · rs1275322585 · VCV3044565

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Conditions

KY-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.7	GERP 0.74, phastCons 1
Overall
CADD	10.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/91,010 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000434% 7/1,613,286 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,753
European (non-Finnish)	0.000254%	393,176

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: KY
Protein: p.Ala591=
Coding: c.1773C>T
MANE Select: NM_001353108 · reported on NM_178554
dbSNP: rs1275322585
Type: single nucleotide variant
Location: chr3:134603792 (GRCh38)

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

Disease context

KY-related disorder

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/ky-p-ala591 (accessed [today's date]).

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