Is PRRX1 p.Ser63= (c.189C>T) pathogenic?

PRRX1 p.Ser63= (c.189C>T) is classified Likely benign in PRRX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-19). Very rare (popmax 0.004%, afr).

How common is PRRX1 p.Ser63= (c.189C>T) in the general population?

PRRX1 p.Ser63= (c.189C>T) is very rare (popmax 0.004%, afr) (gnomAD).

PRRX1 p.Ser63=

c.189C>T · VCV4921189

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 3.1	GERP 1.1, phastCons 1
Overall
CADD	13.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,010 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00205% 33/1,612,074 alleles · very rare exomes 27/1,459,758 · genomes 6/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,003
European (non-Finnish)	0.00254%	39,314

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: PRRX1
Protein: p.Ser63=
Coding: c.189C>T
MANE Select: NM_022716
Type: single nucleotide variant
Location: chr1:170664407 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 66.38
Residue 63: the 'disordered' region

Full PRRX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRRX1 p.Arg62Gln Benign ★★ same type
PRRX1 p.Leu70= Likely benign ★★ same type
PRRX1 p.Ser104Gly Benign/Likely benign ★★ same type
PRRX1 p.Arg124Ter Pathogenic ★ same type
PRRX1 c.418-1G>A Uncertain significance ★ same type
PRRX1 c.-13G>T Uncertain significance ★ same type
PRRX1 p.Ala158Thr Uncertain significance ★ same type
PRRX1 p.Ala184Thr 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/prrx1-p-ser63 (accessed [today's date]).

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