Is XK p.Ser140= (c.420G>A) pathogenic?

XK p.Ser140= (c.420G>A) is classified Benign/Likely benign in XK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0232%, mid); Associated with Inborn genetic diseases.

What condition is associated with XK p.Ser140= (c.420G>A)?

XK p.Ser140= (c.420G>A) is associated with Inborn genetic diseases (ClinVar).

How common is XK p.Ser140= (c.420G>A) in the general population?

XK p.Ser140= (c.420G>A) is ultra-rare (popmax 0.0232%, mid) (gnomAD).

XK p.Ser140=

c.420G>A · rs147126623 · VCV2918663

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0232% Middle Eastern · 1/4,317 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0132% 157/1,189,519 alleles · ultra-rare exomes 137/1,077,371 · genomes 20/112,148 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0232%	4,317
African / African-American	0.0176%	5,676
European (non-Finnish)	0.0156%	6,402
Remaining individualsnot grpmax-eligible	0.0107%	9,362
East Asian	0.00609%	16,414
Finnishnot grpmax-eligible	0.00221%	45,338

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: XK
Protein: p.Ser140=
Coding: c.420G>A
MANE Select: NM_021083
dbSNP: rs147126623
Type: single nucleotide variant
Location: chrX:37694460 (GRCh38)
Structure: AlphaFold pLDDT 81.89 · 1 PDB
Residue 140: a UniProt-annotated variant site (in mclds)

Full XK 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

Similar variants

XK p.Arg138Trp Uncertain significance ★★ ⚠ same condition
XK p.Asn244Ser Uncertain significance ★★ ⚠ same condition
XK p.Glu265Gly Uncertain significance ★★ ⚠ same condition
XK p.Leu185Ser Uncertain significance ★★ ⚠ same condition
XK p.Ser415Ala Uncertain significance ★★ ⚠ same condition
XK p.Lys339Ter Pathogenic ★ same condition
XK p.Ala149Val Uncertain significance ★ same condition
XK p.Asp418Tyr Uncertain significance ★ ⚠ same condition

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/xk-p-ser140 (accessed [today's date]).

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