Is TSR2 p.Asp78= (c.234T>C) pathogenic?

TSR2 p.Asp78= (c.234T>C) is classified Benign/Likely benign in TSR2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-29). Low-frequency (popmax 2.74%, mid); Associated with Diamond-Blackfan anemia 14 with mandibulofacial dysostosis.

What condition is associated with TSR2 p.Asp78= (c.234T>C)?

TSR2 p.Asp78= (c.234T>C) is associated with Diamond-Blackfan anemia 14 with mandibulofacial dysostosis (ClinVar).

How common is TSR2 p.Asp78= (c.234T>C) in the general population?

TSR2 p.Asp78= (c.234T>C) is low-frequency (popmax 2.74%, mid) (gnomAD).

How is Diamond-Blackfan anemia inherited?

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

TSR2 p.Asp78=

c.234T>C · rs36032873 · VCV709009

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.74%, mid)

Conditions

Diamond-Blackfan anemia 14 with mandibulofacial dysostosis

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 0.31	GERP -0.014, phastCons 1
Overall
CADD	4.286	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.74% Middle Eastern · 119/4,338 alleles

Filtering AF 2.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.19%

Overall 0.434% 5,234/1,205,507 alleles · low-frequency exomes 4,716/1,093,692 · genomes 518/111,815 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.74%	36
Amishnot grpmax-eligible	1.76%	57
Ashkenazi Jewishnot grpmax-eligible	0.798%	125
Finnishnot grpmax-eligible	0.62%	161
Remaining individualsnot grpmax-eligible	0.584%	171
European (non-Finnish)	0.445%	224
Admixed American	0.442%	226
South Asian	0.197%	509
African / African-American	0.13%	770

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: TSR2
Protein: p.Asp78=
Coding: c.234T>C
MANE Select: NM_058163
dbSNP: rs36032873
Type: single nucleotide variant
Location: chrX:54443461 (GRCh38)
Structure: AlphaFold pLDDT 74.60

Full TSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Diamond-Blackfan anemia 14 with mandibulofacial dysostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Diamond-Blackfan anemia (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

TSR2 p.Glu64Gly Pathogenic ★ same condition
TSR2 p.Ala8Pro Uncertain significance ★★ ⚠ same type
TSR2 p.Arg56Cys Uncertain significance ★★ ⚠ same type
TSR2 p.Asn75Asp Uncertain significance ★★ ⚠ same type
TSR2 p.Glu6Gly Uncertain significance ★★ ⚠ same type
TSR2 p.Gly35Ala Uncertain significance ★★ ⚠ same type
TSR2 p.His98Tyr Uncertain significance ★★ ⚠ same type
FGD1 p.Phe873= Benign/Likely benign ★★ 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/tsr2-p-asp78 (accessed [today's date]).

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