Is PKHD1 p.Ser403= (c.1209T>C) pathogenic?

PKHD1 p.Ser403= (c.1209T>C) is classified Likely benign in PKHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-17). Ultra-rare (popmax 0.0121%, sas); Associated with autosomal recessive polycystic kidney disease.

What condition is associated with PKHD1 p.Ser403= (c.1209T>C)?

PKHD1 p.Ser403= (c.1209T>C) is associated with autosomal recessive polycystic kidney disease (ClinVar).

How common is PKHD1 p.Ser403= (c.1209T>C) in the general population?

PKHD1 p.Ser403= (c.1209T>C) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

How is Autosomal recessive polycystic kidney disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PKHD1 p.Ser403=

c.1209T>C · rs749529299 · VCV1079194

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

autosomal recessive polycystic kidney disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.85	GERP -3.3, phastCons 0.009
Overall
CADD	7.176	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/90,582 alleles

Filtering AF 0.0068% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00524%

Overall 0.00245% 39/1,589,194 alleles · ultra-rare exomes 39/1,436,872 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,235
European (non-Finnish)	0.00242%	41,330

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: PKHD1
Protein: p.Ser403=
Coding: c.1209T>C
MANE Select: NM_138694
dbSNP: rs749529299
Type: single nucleotide variant
Location: chr6:52059952 (GRCh38)
Gene constraint: LOEUF 0.783 · pLI <0.01 (gnomAD)
Residue 403: the pa14 domain

Full PKHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive polycystic kidney disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive polycystic kidney disease (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

PKHD1 p.Ser403Asn Uncertain significance ★ same residue
PKHD1 p.Ser403Thr Uncertain significance ★ same residue
PKHD1 c.11174+2T>C Likely pathogenic ★★ same condition
PKHD1 c.11310+1G>C Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.11398+2T>C Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.11507-1G>A Likely pathogenic ★★ same condition
PKHD1 c.11665+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKHD1 c.1233+1G>A Pathogenic/Likely pathogenic ★★ 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/pkhd1-p-ser403 (accessed [today's date]).

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