Is PTPRM p.Pro555Ser (c.1663C>T) pathogenic?

PTPRM p.Pro555Ser (c.1663C>T) is classified Uncertain significance in PTPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely pathogenic (0.8669); Absent from gnomAD v4.1.

How common is PTPRM p.Pro555Ser (c.1663C>T) in the general population?

PTPRM p.Pro555Ser (c.1663C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRM p.Pro555Ser (c.1663C>T)?

AlphaMissense predicts likely pathogenic (score 0.8669) — an in-silico prediction, not a clinical call.

PTPRM p.Pro555Ser

c.1663C>T · rs2510179963 · VCV2529043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8669 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8669	likely pathogenic
REVEL	0.648	pathogenic-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 336 kb · p 3.6e-11 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTPRM
Protein: p.Pro555Ser
Coding: c.1663C>T
MANE Select: NM_001105244
dbSNP: rs2510179963
Type: single nucleotide variant
Location: chr18:8085782 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.38 · 5 PDB
Residue 555: the fibronectin type-iii 3 domain

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

Similar variants

PTPRM c.664-9T>C Benign/Likely benign ★★ same type
PTPRM p.Ala748= Benign ★★ same type
PTPRM p.Ser39Arg Benign ★★ same type
PTPRM p.Thr445= Benign ★★ same type
PTPRM p.Val333= Benign ★★ same type
PTPRM p.Ala1128Gly Uncertain significance ★ ⚠ same type
PTPRM p.Ala1163Glu Uncertain significance ★ ⚠ same type
PTPRM p.Ala1163Val 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/ptprm-p-pro555ser (accessed [today's date]).

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