Is KY p.Ile17Phe (c.49A>T) pathogenic?

KY p.Ile17Phe (c.49A>T) is classified Uncertain significance in KY (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: ambiguous (0.374); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KY p.Ile17Phe (c.49A>T)?

KY p.Ile17Phe (c.49A>T) is associated with Inborn genetic diseases (ClinVar).

How common is KY p.Ile17Phe (c.49A>T) in the general population?

KY p.Ile17Phe (c.49A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about KY p.Ile17Phe (c.49A>T)?

AlphaMissense predicts ambiguous (score 0.374) — an in-silico prediction, not a clinical call.

KY p.Ile17Phe

c.49A>T · VCV3536686

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.374	ambiguous
REVEL	0.638	indeterminate
SaProt	LLR -5.68	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 23 kb · p 0.071 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,490 alleles

Overall 6.84e-05% 1/1,460,998 alleles · very rare

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.Ile17Phe
Coding: c.49A>T
MANE Select: NM_001353108 · reported on NM_178554
Type: single nucleotide variant
Location: chr3:134650912 (GRCh38)

Full KY 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

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-ile17phe (accessed [today's date]).

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