Is XYLT2 p.Arg71= (c.211C>A) pathogenic?

XYLT2 p.Arg71= (c.211C>A) is classified Likely benign in XYLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-27). Very rare (popmax 0.00272%, afr).

How common is XYLT2 p.Arg71= (c.211C>A) in the general population?

XYLT2 p.Arg71= (c.211C>A) is very rare (popmax 0.00272%, afr) (gnomAD).

XYLT2 p.Arg71=

c.211C>A · rs773702784 · VCV2907949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00272%, afr)

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 1.9	GERP 1.4, phastCons 0.93
Overall
CADD	9.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00272% African / African-American · 2/73,660 alleles

Filtering AF 0.00193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00224% 35/1,561,456 alleles · very rare exomes 29/1,409,272 · genomes 6/152,184 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0033%	30,264
African / African-Americangrpmax	0.00272%	36,830
European (non-Finnish)	0.00269%	37,168

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg71=
Coding: c.211C>A
MANE Select: NM_022167
dbSNP: rs773702784
Type: single nucleotide variant
Location: chr17:50353705 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79
Residue 71: the 'disordered' region

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

Similar variants

XYLT2 p.Arg71Gln Uncertain significance ★ ⚠ same residue
XYLT2 p.Arg563Cys Likely pathogenic ★★ same type
XYLT2 p.Ala254Val Uncertain significance ★★ ⚠ same type
XYLT2 p.Ala543Thr Uncertain significance ★★ ⚠ same type
XYLT2 p.Ala570Thr Uncertain significance ★★ ⚠ same type
XYLT2 p.Ala614Val Uncertain significance ★★ ⚠ same type
XYLT2 p.Ala807Val Uncertain significance ★★ ⚠ same type
XYLT2 p.Arg104Lys 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/xylt2-p-arg71 (accessed [today's date]).

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