Is XYLT2 p.Ala797= (c.2391C>T) pathogenic?

XYLT2 p.Ala797= (c.2391C>T) is classified Likely benign in XYLT2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-30). Rare (popmax 0.17%, nfe); Associated with osteogenesis imperfecta.

What condition is associated with XYLT2 p.Ala797= (c.2391C>T)?

XYLT2 p.Ala797= (c.2391C>T) is associated with osteogenesis imperfecta (ClinVar).

How common is XYLT2 p.Ala797= (c.2391C>T) in the general population?

XYLT2 p.Ala797= (c.2391C>T) is rare (popmax 0.17%, nfe) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

XYLT2 p.Ala797=

c.2391C>T · rs141527159 · VCV708827

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.17%, nfe)

Conditions

osteogenesis imperfecta

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 -0.002	GERP -2, phastCons 0.74
Overall
CADD	3.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.17% European (non-Finnish) · 2,005/1,179,970 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.132% 2,134/1,613,944 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.17%	589
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Middle Eastern	0.0825%	1,212
Admixed American	0.055%	1,819
African / African-American	0.0293%	3,411
South Asian	0.0121%	8,281
Finnishnot grpmax-eligible	0.0094%	10,643

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.Ala797=
Coding: c.2391C>T
MANE Select: NM_022167
dbSNP: rs141527159
Type: single nucleotide variant
Location: chr17:50360084 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79
Residue 797: a disulfide bond

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.Arg120His Benign/Likely benign ★★ same condition
XYLT2 p.Asp56Asn 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-ala797 (accessed [today's date]).

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