Is PKDCC p.Ser492Phe (c.1475C>T) pathogenic?

PKDCC p.Ser492Phe (c.1475C>T) is classified Uncertain significance in PKDCC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-27). AlphaMissense: likely benign (0.1272); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with PKDCC p.Ser492Phe (c.1475C>T)?

PKDCC p.Ser492Phe (c.1475C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PKDCC p.Ser492Phe (c.1475C>T) in the general population?

PKDCC p.Ser492Phe (c.1475C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about PKDCC p.Ser492Phe (c.1475C>T)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

PKDCC p.Ser492Phe

c.1475C>T · rs772850359 · VCV1490731

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.55, phastCons 0.029
Regional constraint	o/e 1.10	unconstrained · MANE · 9,485 bp · p 0.012 · regional, not allelic
Overall
CADD	21.8	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,920 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,613,604 alleles · very rare exomes 2/1,461,394 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,730
South Asian	0.0011%	91,010

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: PKDCC
Protein: p.Ser492Phe
Coding: c.1475C>T
MANE Select: NM_138370
dbSNP: rs772850359
Type: single nucleotide variant
Location: chr2:42057681 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96
Residue 492: a UniProt-annotated variant site (in rlsdf); the protein kinase domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PKDCC p.Ala299Thr Uncertain significance ★★ ⚠ same condition
PKDCC p.Arg280Cys Uncertain significance ★★ ⚠ same condition
PKDCC p.Arg338Gln Uncertain significance ★★ ⚠ same condition
PKDCC p.Arg393Gln Uncertain significance ★★ ⚠ same condition
PKDCC p.Asp295Glu Uncertain significance ★★ ⚠ same condition
PKDCC p.Asp89His Uncertain significance ★★ ⚠ same condition
PKDCC p.Cys331Arg Uncertain significance ★★ ⚠ same condition
PKDCC p.Glu380Lys 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/pkdcc-p-ser492phe (accessed [today's date]).

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