Is PTK2 p.Arg349= (c.1047G>T) pathogenic?

PTK2 p.Arg349= (c.1047G>T) is classified Benign in PTK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.48%, sas).

How common is PTK2 p.Arg349= (c.1047G>T) in the general population?

PTK2 p.Arg349= (c.1047G>T) is low-frequency (popmax 1.48%, sas) (gnomAD).

PTK2 p.Arg349=

c.1047G>T · rs139753749 · VCV789195

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.48%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.044	GERP -2.5, phastCons 0.69
Overall
CADD	6.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.48% South Asian · 1,351/91,056 alleles

Filtering AF 1.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.828% 13,358/1,613,792 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.75%	57
South Asiangrpmax	1.48%	67
Ashkenazi Jewishnot grpmax-eligible	1.21%	82
European (non-Finnish)	0.893%	112
Remaining individualsnot grpmax-eligible	0.746%	134
Middle Eastern	0.561%	178
Admixed American	0.433%	231
Finnishnot grpmax-eligible	0.364%	275
African / African-American	0.14%	714
East Asian	0.00446%	22,440

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PTK2
Protein: p.Arg349=
Coding: c.1047G>T
MANE Select: NM_001352702
dbSNP: rs139753749
Type: single nucleotide variant
Location: chr8:140800505 (GRCh38)
Gene constraint: LOEUF 0.399 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.10 · 40 PDB
Residue 349: the ferm domain; an α-helix

Full PTK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTK2 p.Arg855Ter Uncertain significance ★★ same type
PTK2 c.*705T>A Benign ★★ same type
PTK2 p.Asp703= Benign ★★ same type
PTK2 p.Glu870= Benign/Likely benign ★★ same type
PTK2 p.Pro690= Benign ★★ same type
PTK2 p.Ser355= Benign ★★ same type
PTK2 p.Tyr969= Benign ★★ same type
PTK2 p.Val215= Benign ★★ 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/ptk2-p-arg349 (accessed [today's date]).

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