Is KPTN p.Pro13= (c.39G>A) pathogenic?

KPTN p.Pro13= (c.39G>A) is classified Likely benign in KPTN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). Ultra-rare (popmax 0.0527%, sas); Associated with macrocephaly-developmental delay syndrome.

What condition is associated with KPTN p.Pro13= (c.39G>A)?

KPTN p.Pro13= (c.39G>A) is associated with macrocephaly-developmental delay syndrome (ClinVar).

How common is KPTN p.Pro13= (c.39G>A) in the general population?

KPTN p.Pro13= (c.39G>A) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

KPTN p.Pro13=

c.39G>A · rs779502366 · VCV2182364

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Conditions

macrocephaly-developmental delay syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.6
Overall
CADD	10.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0527% South Asian · 48/91,032 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00312% 50/1,601,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0527%	1,897
Middle Eastern	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.0016%	62,388

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: KPTN
Protein: p.Pro13=
Coding: c.39G>A
MANE Select: NM_007059
dbSNP: rs779502366
Type: single nucleotide variant
Location: chr19:47484122 (GRCh38)
Gene constraint: LOEUF 0.988 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.56 · 8 PDB

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

Disease context

macrocephaly-developmental delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KPTN p.Ser259Ter Pathogenic ★★ same condition
KPTN c.1183-3C>G Uncertain significance ★★ same condition
KPTN p.Ala260Asp Uncertain significance ★★ ⚠ same condition
KPTN p.Ala261Thr Uncertain significance ★★ ⚠ same condition
KPTN p.Ala329Pro Uncertain significance ★★ ⚠ same condition
KPTN p.Ala35Thr Uncertain significance ★★ ⚠ same condition
KPTN p.Arg293Gln Uncertain significance ★★ ⚠ same condition
KPTN p.Arg54His 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/kptn-p-pro13 (accessed [today's date]).

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