Is XYLT2 p.Ser641= (c.1923C>T) pathogenic?

XYLT2 p.Ser641= (c.1923C>T) is classified Conflicting classifications of pathogenicity in XYLT2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-01). Rare (popmax 0.103%, sas); Associated with osteogenesis imperfecta.

What condition is associated with XYLT2 p.Ser641= (c.1923C>T)?

XYLT2 p.Ser641= (c.1923C>T) is associated with osteogenesis imperfecta (ClinVar).

How common is XYLT2 p.Ser641= (c.1923C>T) in the general population?

XYLT2 p.Ser641= (c.1923C>T) is rare (popmax 0.103%, sas) (gnomAD).

How is Osteogenesis imperfecta inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

XYLT2 p.Ser641=

c.1923C>T · rs778642140 · VCV1702076

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.103%, sas)

Conditions

osteogenesis imperfecta

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 6	GERP 0.56, phastCons 1
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% South Asian · 93/89,930 alleles

Filtering AF 0.0864% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0801%

Overall 0.0243% 389/1,599,860 alleles · rare exomes 361/1,447,530 · genomes 28/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.103%	967
Middle Eastern	0.0735%	1,361
European (non-Finnish)	0.024%	4,169
Remaining individualsnot grpmax-eligible	0.0145%	6,883
African / African-American	0.00134%	74,748

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: XYLT2
Protein: p.Ser641=
Coding: c.1923C>T
MANE Select: NM_022167
dbSNP: rs778642140
Type: single nucleotide variant
Location: chr17:50357234 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79

Full XYLT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

XYLT2 p.Ala570Thr Uncertain significance ★★ ⚠ same condition
XYLT2 p.Ala807Val Uncertain significance ★★ ⚠ same condition
XYLT2 p.Pro115Leu Uncertain significance ★★ ⚠ same condition
XYLT2 p.Val165Met Uncertain significance ★★ ⚠ same condition
XYLT2 p.Val287Met Uncertain significance ★★ ⚠ same condition
XYLT2 c.1089-9T>C Benign/Likely benign ★★ same condition
XYLT2 p.Ala797= Likely benign ★★ same condition
XYLT2 p.Arg120His Benign/Likely benign ★★ 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/xylt2-p-ser641 (accessed [today's date]).

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