Is TPRN p.Pro400= (c.1200C>T) pathogenic?

TPRN p.Pro400= (c.1200C>T) is classified Likely benign in TPRN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-23). Very rare (popmax 0.00232%, nfe).

How common is TPRN p.Pro400= (c.1200C>T) in the general population?

TPRN p.Pro400= (c.1200C>T) is very rare (popmax 0.00232%, nfe) (gnomAD).

TPRN p.Pro400=

c.1200C>T · rs746736124 · VCV2884638

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00232%, nfe)

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 -0.31	GERP -1.8
Overall
CADD	5.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00232% European (non-Finnish) · 27/1,162,028 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00184% 29/1,576,840 alleles · very rare exomes 25/1,424,636 · genomes 4/152,204 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00232%	43,038
Admixed American	0.00183%	54,594
Remaining individualsnot grpmax-eligible	0.00164%	61,062

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: TPRN
Protein: p.Pro400=
Coding: c.1200C>T
MANE Select: NM_001128228
dbSNP: rs746736124
Type: single nucleotide variant
Location: chr9:137199512 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.27 · 1 PDB

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

Similar variants

TPRN p.Pro400His Uncertain significance ★ ⚠ same residue
TPRN p.Gln414Ter Pathogenic ★★ same type
TPRN c.1725+5G>A Uncertain significance ★★ same type
TPRN p.Ala191Val Uncertain significance ★★ ⚠ same type
TPRN p.Ala302Asp Uncertain significance ★★ ⚠ same type
TPRN p.Ala390Ser Uncertain significance ★★ ⚠ same type
TPRN p.Ala695Thr Uncertain significance ★★ ⚠ same type
TPRN p.Arg231Trp 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/tprn-p-pro400 (accessed [today's date]).

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