Is PRRX1 p.Pro185Thr (c.553C>A) pathogenic?

PRRX1 p.Pro185Thr (c.553C>A) is classified Uncertain significance in PRRX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely benign (0.1473); Very rare (popmax 0.000657%); Associated with Inborn genetic diseases.

What condition is associated with PRRX1 p.Pro185Thr (c.553C>A)?

PRRX1 p.Pro185Thr (c.553C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PRRX1 p.Pro185Thr (c.553C>A) in the general population?

PRRX1 p.Pro185Thr (c.553C>A) is very rare (popmax 0.000657%) (gnomAD).

What do computational predictors say about PRRX1 p.Pro185Thr (c.553C>A)?

AlphaMissense predicts likely benign (score 0.1473) — an in-silico prediction, not a clinical call.

PRRX1 p.Pro185Thr

c.553C>A · VCV3783969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000657%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1473	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP -1.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 72 kb · p 0.021 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000657%

Overall 0.000657% 1/152,132 alleles · very rare

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.Pro185Thr
Coding: c.553C>A
MANE Select: NM_022716
Type: single nucleotide variant
Location: chr1:170726355 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 66.38

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRRX1 p.Ala158Thr Uncertain significance ★ same condition
PRRX1 p.Ala184Thr Uncertain significance ★ ⚠ same condition
PRRX1 p.Ala201Thr Uncertain significance ★ ⚠ same condition
PRRX1 p.Ala30Glu Uncertain significance ★ ⚠ same condition
PRRX1 p.Arg11Trp Uncertain significance ★ ⚠ same condition
PRRX1 p.Gln240His Uncertain significance ★ ⚠ same condition
PRRX1 p.Gly17Ser Uncertain significance ★ ⚠ same condition
PRRX1 p.Ile179Val Uncertain significance ★ ⚠ same condition

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-pro185thr (accessed [today's date]).

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