Is KY p.Ser39= (c.117G>C) pathogenic?

KY p.Ser39= (c.117G>C) is classified Likely benign in KY (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-01). Ultra-rare (popmax 0.0497%, mid).

How common is KY p.Ser39= (c.117G>C) in the general population?

KY p.Ser39= (c.117G>C) is ultra-rare (popmax 0.0497%, mid) (gnomAD).

KY p.Ser39=

c.117G>C · rs748047746 · VCV737425

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 0.76	GERP -0.85, phastCons 0.98
Overall
CADD	11.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% Middle Eastern · 3/6,038 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00611% 98/1,605,016 alleles · ultra-rare exomes 92/1,452,926 · genomes 6/152,090 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0497%	2,013
Remaining individualsnot grpmax-eligible	0.0113%	8,849
European (non-Finnish)	0.00732%	13,664
Admixed American	0.00168%	59,452
African / African-American	0.00135%	74,318

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.Ser39=
Coding: c.117G>C
MANE Select: NM_178554
dbSNP: rs748047746
Type: single nucleotide variant
Location: chr3:134650844 (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-ser39 (accessed [today's date]).

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