Is PTPN4 p.Ser807Arg (c.2421T>A) pathogenic?

PTPN4 p.Ser807Arg (c.2421T>A) is classified Uncertain significance in PTPN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely benign (0.247); Very rare (popmax 0.00353%, amr); Associated with Inborn genetic diseases.

What condition is associated with PTPN4 p.Ser807Arg (c.2421T>A)?

PTPN4 p.Ser807Arg (c.2421T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PTPN4 p.Ser807Arg (c.2421T>A) in the general population?

PTPN4 p.Ser807Arg (c.2421T>A) is very rare (popmax 0.00353%, amr) (gnomAD).

What do computational predictors say about PTPN4 p.Ser807Arg (c.2421T>A)?

AlphaMissense predicts likely benign (score 0.247) — an in-silico prediction, not a clinical call.

PTPN4 p.Ser807Arg

c.2421T>A · VCV3311459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.247 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00353%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.247	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -0.67, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 20 kb · p 5.8e-12 · regional, not allelic
Overall
CADD	22.0	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 0.00353% Admixed American · 2/56,584 alleles

Filtering AF 0.000586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000187% 3/1,602,674 alleles · very rare exomes 3/1,450,366 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00353%	28,292
Remaining individualsnot grpmax-eligible	0.00161%	61,986

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: PTPN4
Protein: p.Ser807Arg
Coding: c.2421T>A
MANE Select: NM_002830
Type: single nucleotide variant
Location: chr2:119965508 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 8 PDB
Residue 807: the tyrosine-protein phosphatase domain; a β-strand

Full PTPN4 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

PTPN4 p.Arg249Ter Pathogenic ★★ same condition
PTPN4 p.Arg22Ter Likely pathogenic ★ same condition
PTPN4 p.Arg6Ter Likely pathogenic ★ same condition
PTPN4 p.Leu64Ter Pathogenic ★ same condition
PTPN4 p.Ala146Thr Uncertain significance ★ ⚠ same condition
PTPN4 p.Ala189Gly Uncertain significance ★ ⚠ same condition
PTPN4 p.Ala42Asp Uncertain significance ★ ⚠ same condition
PTPN4 p.Ala907Thr 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/ptpn4-p-ser807arg (accessed [today's date]).

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