Is KY p.Leu41= (c.123G>A) pathogenic?

KY p.Leu41= (c.123G>A) is classified Likely benign in KY (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0509%, sas).

How common is KY p.Leu41= (c.123G>A) in the general population?

KY p.Leu41= (c.123G>A) is ultra-rare (popmax 0.0509%, sas) (gnomAD).

KY p.Leu41=

c.123G>A · rs745313504 · VCV2654166

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, sas)

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 0.49	GERP 0.56, phastCons 0.7
Overall
CADD	12.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0509% South Asian · 46/90,432 alleles

Filtering AF 0.0392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.00387% 62/1,603,342 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0509%	1,966
Remaining individualsnot grpmax-eligible	0.00646%	15,474
Admixed American	0.00337%	29,709
European (non-Finnish)	0.000852%	117,391

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.Leu41=
Coding: c.123G>A
MANE Select: NM_001353108 · reported on NM_178554
dbSNP: rs745313504
Type: single nucleotide variant
Location: chr3:134650838 (GRCh38)

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

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-leu41 (accessed [today's date]).

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