Is KPTN p.Val65= (c.195G>A) pathogenic?

KPTN p.Val65= (c.195G>A) is classified Likely benign in KPTN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-03). Very rare (popmax 0.00668%, eas); Associated with macrocephaly-developmental delay syndrome.

What condition is associated with KPTN p.Val65= (c.195G>A)?

KPTN p.Val65= (c.195G>A) is associated with macrocephaly-developmental delay syndrome (ClinVar).

How common is KPTN p.Val65= (c.195G>A) in the general population?

KPTN p.Val65= (c.195G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

KPTN p.Val65=

c.195G>A · rs1212228151 · VCV1144504

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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 0.22	GERP -0.56, phastCons 0.97
Overall
CADD	11.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,888 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000434% 7/1,613,794 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
Remaining individualsnot grpmax-eligible	0.0032%	31,242
South Asian	0.0022%	45,541

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.Val65=
Coding: c.195G>A
MANE Select: NM_007059
dbSNP: rs1212228151
Type: single nucleotide variant
Location: chr19:47483966 (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-val65 (accessed [today's date]).

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