Is PTPRM p.Ile172Val (c.514A>G) pathogenic?

PTPRM p.Ile172Val (c.514A>G) is classified Uncertain significance in PTPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.0901); Ultra-rare (popmax 0.03%, amr).

How common is PTPRM p.Ile172Val (c.514A>G) in the general population?

PTPRM p.Ile172Val (c.514A>G) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about PTPRM p.Ile172Val (c.514A>G)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

PTPRM p.Ile172Val

c.514A>G · rs751358939 · VCV3149495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 382 kb · p 0.0078 · regional, not allelic
Overall
CADD	18.97	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 0.03% Admixed American · 18/60,010 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00242% 39/1,613,524 alleles · ultra-rare exomes 35/1,461,296 · genomes 4/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,334
South Asian	0.0022%	45,537
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00144%	69,382
African / African-American	0.00133%	74,928

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: PTPRM
Protein: p.Ile172Val
Coding: c.514A>G
MANE Select: NM_001105244
dbSNP: rs751358939
Type: single nucleotide variant
Location: chr18:7906550 (GRCh38)
Gene constraint: LOEUF 0.334 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.38 · 5 PDB
Residue 172: the mam domain; a β-strand

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-ile172val (accessed [today's date]).

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