Is KL p.Ser742= (c.2226C>G) pathogenic?

KL p.Ser742= (c.2226C>G) is classified Likely benign in KL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-20). Ultra-rare (popmax 0.0513%, eas).

How common is KL p.Ser742= (c.2226C>G) in the general population?

KL p.Ser742= (c.2226C>G) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

KL p.Ser742=

c.2226C>G · rs201355613 · VCV2903903

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

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 -0.58	GERP -0.93
Overall
CADD	6.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0513% East Asian · 23/44,878 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00142% 23/1,614,172 alleles · ultra-rare exomes 21/1,461,890 · genomes 2/152,282 · joint denominator

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: KL
Protein: p.Ser742=
Coding: c.2226C>G
MANE Select: NM_004795
dbSNP: rs201355613
Type: single nucleotide variant
Location: chr13:33061305 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 6 PDB
Residue 742: the 'glycosyl hydrolase-1 2' region

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

Similar variants

KL c.1331-3C>A Uncertain significance ★★ same type
KL p.Ala3Thr Uncertain significance ★★ ⚠ same type
KL p.Ala50Val Uncertain significance ★★ ⚠ same type
KL p.Ala656Thr Uncertain significance ★★ ⚠ same type
KL p.Ala663Thr Uncertain significance ★★ ⚠ same type
KL p.Ala987Thr Uncertain significance ★★ ⚠ same type
KL p.Arg179Trp Uncertain significance ★★ ⚠ same type
KL p.Arg181Gln 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/kl-p-ser742 (accessed [today's date]).

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