Is PTK2B p.Pro413= (c.1239C>T) pathogenic?

PTK2B p.Pro413= (c.1239C>T) is classified Benign in PTK2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-31). Common (popmax 8.95%, afr) — too common for a highly-penetrant pathogenic allele.

PTK2B p.Pro413=

Q: How common is PTK2B p.Pro413= (c.1239C>T) in the general population?

PTK2B p.Pro413= (c.1239C>T) is common (popmax 8.95%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1239C>T · rs55853846 · VCV776301

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.95%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.062	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.6
Overall
CADD	0.079	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.95% African / African-American · 6,717/75,038 alleles

Filtering AF 8.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.7%

Overall 0.481% 7,767/1,614,000 alleles · common exomes 3,854/1,461,692 · genomes 3,913/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.95%	11
Admixed American	0.676%	148
Remaining individualsnot grpmax-eligible	0.661%	151
Middle Eastern	0.61%	164
South Asian	0.0253%	3,960
European (non-Finnish)	0.0143%	6,982
Finnishnot grpmax-eligible	0.00313%	31,951

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: PTK2B
Protein: p.Pro413=
Coding: c.1239C>T
MANE Select: NM_173176
dbSNP: rs55853846
Type: single nucleotide variant
Location: chr8:27435789 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 26 PDB

Full PTK2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTK2B p.Gln359Glu Likely benign ★★ same type
PTK2B p.Leu178= Benign ★★ same type
PTK2B p.Thr264Asn Likely benign ★★ same type
PTK2B p.Ala258Thr Uncertain significance ★ ⚠ same type
PTK2B p.Ala345Thr Uncertain significance ★ ⚠ same type
PTK2B p.Ala709Val Uncertain significance ★ ⚠ same type
PTK2B p.Ala799Val Uncertain significance ★ ⚠ same type
PTK2B p.Ala890Thr 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/ptk2b-p-pro413 (accessed [today's date]).

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