Is TPRN p.Phe196= (c.588C>T) pathogenic?

TPRN p.Phe196= (c.588C>T) is classified Likely benign in TPRN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). Very rare (popmax 0.00315%, eas).

How common is TPRN p.Phe196= (c.588C>T) in the general population?

TPRN p.Phe196= (c.588C>T) is very rare (popmax 0.00315%, eas) (gnomAD).

TPRN p.Phe196=

c.588C>T · rs1834781262 · VCV3021424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00315%, eas)

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 3.5	GERP -0.36, phastCons 1
Overall
CADD	9.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00315% East Asian · 1/31,704 alleles

Filtering AF 3.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3e-05%

Overall 0.000241% 3/1,242,856 alleles · very rare exomes 3/1,093,366 · genomes 0/149,490 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00315%	31,704
European (non-Finnish)	0.000201%	496,991

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.Phe196=
Coding: c.588C>T
MANE Select: NM_001128228
dbSNP: rs1834781262
Type: single nucleotide variant
Location: chr9:137200124 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 55.27 · 1 PDB
Residue 196: the 'disordered' region

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

Similar variants

TPRN p.Phe196Leu 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-phe196 (accessed [today's date]).

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