Is PRKCSH p.Pro71Ser (c.211C>T) pathogenic?

PRKCSH p.Pro71Ser (c.211C>T) is classified Uncertain significance in PRKCSH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1054); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRKCSH p.Pro71Ser (c.211C>T)?

PRKCSH p.Pro71Ser (c.211C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRKCSH p.Pro71Ser (c.211C>T) in the general population?

PRKCSH p.Pro71Ser (c.211C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKCSH p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

PRKCSH p.Pro71Ser

c.211C>T · VCV3425153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -7.28	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 4.7	GERP 0.85, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 12 kb · p 0.21 · regional, not allelic
Overall
CADD	23.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKCSH
Protein: p.Pro71Ser
Coding: c.211C>T
MANE Select: NM_001289104
Type: single nucleotide variant
Location: chr19:11437890 (GRCh38)
Gene constraint: LOEUF 0.699 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.33 · 2 PDB
Residue 71: the ldl-receptor class a 1 domain; a UniProt-annotated variant site (in pcld1)

Full PRKCSH 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

PRKCSH p.Arg381Cys Uncertain significance ★★ ⚠ same condition
PRKCSH p.Arg489His Uncertain significance ★★ ⚠ same condition
PRKCSH p.Asn412Ser Uncertain significance ★★ ⚠ same condition
PRKCSH p.Asp375Asn Uncertain significance ★★ ⚠ same condition
PRKCSH p.Asp41Glu Uncertain significance ★★ ⚠ same condition
PRKCSH p.Gln209His Uncertain significance ★★ ⚠ same condition
PRKCSH p.Glu132Lys Uncertain significance ★★ ⚠ same condition
PRKCSH p.Glu330Lys 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/prkcsh-p-pro71ser (accessed [today's date]).

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