Is TPPP p.Arg57= (c.171C>T) pathogenic?

TPPP p.Arg57= (c.171C>T) is classified Benign in TPPP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele.

TPPP p.Arg57=

Q: How common is TPPP p.Arg57= (c.171C>T) in the general population?

TPPP p.Arg57= (c.171C>T) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.171C>T · rs7737292 · VCV780940

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.1	GERP -2.2
Overall
CADD	6.593	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% African / African-American · 7,557/75,042 alleles

Filtering AF 9.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.8%

Overall 0.546% 8,809/1,612,726 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Middle Eastern	0.99%	101
Remaining individualsnot grpmax-eligible	0.792%	126
Admixed American	0.622%	161
South Asian	0.171%	584
European (non-Finnish)	0.0142%	7,065
East Asian	0.00223%	44,866

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: TPPP
Protein: p.Arg57=
Coding: c.171C>T
MANE Select: NM_007030
dbSNP: rs7737292
Type: single nucleotide variant
Location: chr5:677890 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 3 PDB
Residue 57: the 'mediates interaction with limk1' region

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

Similar variants

TPPP p.Gly39Ala Benign ★★ same type
TPPP p.Pro19= Benign/Likely benign ★★ same type
TPPP p.Ala38Val Uncertain significance ★ ⚠ same type
TPPP p.Ala54Thr Uncertain significance ★ ⚠ same type
TPPP p.Ala8Ser Uncertain significance ★ ⚠ same type
TPPP p.Arg26Gln Uncertain significance ★ ⚠ same type
TPPP p.Gly39Ser Uncertain significance ★ ⚠ same type
TPPP p.Gly73Ser 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/tppp-p-arg57 (accessed [today's date]).

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