Is PKD1 p.Ser623= (c.1869C>T) pathogenic?

PKD1 p.Ser623= (c.1869C>T) is classified Uncertain significance in PKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). Rare (popmax 0.129%, sas); Associated with polycystic kidney disease 1.

What condition is associated with PKD1 p.Ser623= (c.1869C>T)?

PKD1 p.Ser623= (c.1869C>T) is associated with polycystic kidney disease 1 (ClinVar).

How common is PKD1 p.Ser623= (c.1869C>T) in the general population?

PKD1 p.Ser623= (c.1869C>T) is rare (popmax 0.129%, sas) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

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

PKD1 p.Ser623=

c.1869C>T · VCV3891995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.129%, sas)

Conditions

polycystic kidney disease 1

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 -0.9	GERP -1.9
Overall
CADD	0.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% South Asian · 116/90,188 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00919% 147/1,599,746 alleles · rare exomes 132/1,447,520 · genomes 15/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.129%	777
Remaining individualsnot grpmax-eligible	0.00646%	15,471
European (non-Finnish)	0.00213%	47,005
Admixed American	0.00168%	59,490
African / African-American	0.00134%	74,434

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: PKD1
Protein: p.Ser623=
Coding: c.1869C>T
MANE Select: NM_001009944
Type: single nucleotide variant
Location: chr16:2115606 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 623: the 'disordered' region

Full PKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

polycystic kidney disease 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant polycystic kidney disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PKD1 p.Ser623Arg Uncertain significance ★★ ⚠ same residue
PKD1 c.10619-2A>G Pathogenic ★★ same condition
PKD1 c.10821+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.10821+2T>G Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.11017-10C>A Pathogenic/Likely pathogenic ★★ same condition
PKD1 c.11017-25A>C Likely pathogenic ★★ same condition
PKD1 c.11017-25A>G Likely pathogenic ★★ same condition
PKD1 c.11269+1G>C 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/pkd1-p-ser623 (accessed [today's date]).

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