Is PKDCC p.Pro238Ser (c.712C>T) pathogenic?

PKDCC p.Pro238Ser (c.712C>T) is classified Uncertain significance in PKDCC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely pathogenic (0.6374); Very rare (popmax 0.000932%, nfe).

How common is PKDCC p.Pro238Ser (c.712C>T) in the general population?

PKDCC p.Pro238Ser (c.712C>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about PKDCC p.Pro238Ser (c.712C>T)?

AlphaMissense predicts likely pathogenic (score 0.6374) — an in-silico prediction, not a clinical call.

PKDCC p.Pro238Ser

c.712C>T · rs768587129 · VCV1460514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6374	likely pathogenic
REVEL	0.291	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 9,485 bp · p 0.012 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,936 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,776 alleles · very rare exomes 10/1,461,638 · genomes 1/152,138 · joint denominator

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.Pro238Ser
Coding: c.712C>T
MANE Select: NM_138370
dbSNP: rs768587129
Type: single nucleotide variant
Location: chr2:42053311 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96
Residue 238: 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

Similar variants

PKDCC p.Leu262Arg Pathogenic/Likely pathogenic ★★ same type
PKDCC c.640-12G>A Uncertain significance ★★ same type
PKDCC p.Ala299Thr Uncertain significance ★★ ⚠ same type
PKDCC p.Arg280Cys Uncertain significance ★★ ⚠ same type
PKDCC p.Arg338Gln Uncertain significance ★★ ⚠ same type
PKDCC p.Arg393Gln Uncertain significance ★★ ⚠ same type
PKDCC p.Asp295Glu Uncertain significance ★★ ⚠ same type
PKDCC p.Asp89His Uncertain significance ★★ ⚠ same type

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-pro238ser (accessed [today's date]).

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