Is TSEN2 p.Asp213= (c.639T>C) pathogenic?

TSEN2 p.Asp213= (c.639T>C) is classified Benign in TSEN2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 5.56%, sas) — too common for a highly-penetrant pathogenic allele; Associated with pontocerebellar hypoplasia.

What condition is associated with TSEN2 p.Asp213= (c.639T>C)?

TSEN2 p.Asp213= (c.639T>C) is associated with pontocerebellar hypoplasia (ClinVar).

TSEN2 p.Asp213=

Q: How common is TSEN2 p.Asp213= (c.639T>C) in the general population?

TSEN2 p.Asp213= (c.639T>C) is common (popmax 5.56%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.639T>C · rs3796329 · VCV137750

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.56%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

pontocerebellar hypoplasia

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 -1.5	GERP -2.9
Overall
CADD	0.851	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.56% South Asian · 4,950/89,066 alleles

Filtering AF 5.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.38%

Overall 1.82% 29,031/1,598,752 alleles · common exomes 25,278/1,446,506 · genomes 3,753/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	5.56%	18
East Asian	4.29%	23
Admixed American	4.11%	24
African / African-American	3.25%	31
Remaining individualsnot grpmax-eligible	2.18%	46
European (non-Finnish)	1.29%	77
Middle Eastern	1.27%	79
Finnishnot grpmax-eligible	1.03%	97
Amishnot grpmax-eligible	0.439%	228
Ashkenazi Jewishnot grpmax-eligible	0.334%	299

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: TSEN2
Protein: p.Asp213=
Coding: c.639T>C
MANE Select: NM_025265
dbSNP: rs3796329
Type: single nucleotide variant
Location: chr3:12503592 (GRCh38)
Gene constraint: LOEUF 1.212 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.63 · 5 PDB

Full TSEN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TSEN2 c.1099+1G>A Likely pathogenic ★★ same condition
TSEN2 p.Tyr19Ter Pathogenic/Likely pathogenic ★★ same condition
TSEN2 p.Ala227Val Uncertain significance ★★ ⚠ same condition
TSEN2 p.Asn282Ser Uncertain significance ★★ ⚠ same condition
TSEN2 p.Asp250Asn Uncertain significance ★★ ⚠ same condition
TSEN2 p.Glu212Ala Uncertain significance ★★ ⚠ same condition
TSEN2 p.Leu234Phe Uncertain significance ★★ ⚠ same condition
TSEN2 p.Phe40Cys 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/tsen2-p-asp213 (accessed [today's date]).

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