Is PKD1 p.Ala1926Val (c.5777C>T) pathogenic?

PKD1 p.Ala1926Val (c.5777C>T) is classified Uncertain significance in PKD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-10). AlphaMissense: likely benign (0.087); Very rare (popmax 0.00246%, nfe); Associated with polycystic kidney disease 1.

What condition is associated with PKD1 p.Ala1926Val (c.5777C>T)?

PKD1 p.Ala1926Val (c.5777C>T) is associated with polycystic kidney disease 1 (ClinVar).

How common is PKD1 p.Ala1926Val (c.5777C>T) in the general population?

PKD1 p.Ala1926Val (c.5777C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

How is Autosomal dominant polycystic kidney disease inherited?

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

What do computational predictors say about PKD1 p.Ala1926Val (c.5777C>T)?

AlphaMissense predicts likely benign (score 0.087) — an in-silico prediction, not a clinical call.

PKD1 p.Ala1926Val

c.5777C>T · rs754890213 · VCV1256447

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

polycystic kidney disease 1

Computational evidence

Protein change
AlphaMissense	0.087	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -3, phastCons 0.95
Regional constraint	o/e 1.08	unconstrained · MANE · 7,908 bp · p 6.5e-05 · regional, not allelic
Overall
CADD	9.327	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,177,644 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.002% 32/1,597,672 alleles · very rare exomes 28/1,445,424 · genomes 4/152,248 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00322%	31,022
European (non-Finnish)grpmax	0.00246%	40,608
Admixed American	0.00167%	59,910

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala1926Val
Coding: c.5777C>T
MANE Select: NM_001009944
dbSNP: rs754890213
Type: single nucleotide variant
Location: chr16:2109390 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1926: a UniProt-annotated variant site (in); the pkd 15 domain

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.Ala1926fs Pathogenic ★ 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-ala1926val (accessed [today's date]).

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