Is KRIT1 p.Arg16Pro (c.47G>C) pathogenic?

KRIT1 p.Arg16Pro (c.47G>C) is classified Conflicting classifications of pathogenicity in KRIT1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-07-05). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with cerebral cavernous malformation.

What condition is associated with KRIT1 p.Arg16Pro (c.47G>C)?

KRIT1 p.Arg16Pro (c.47G>C) is associated with cerebral cavernous malformation (ClinVar).

How common is KRIT1 p.Arg16Pro (c.47G>C) in the general population?

KRIT1 p.Arg16Pro (c.47G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRIT1 p.Arg16Pro (c.47G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

KRIT1 p.Arg16Pro

c.47G>C · rs1313893193 · VCV1008435

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cerebral cavernous malformation

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 1% in KRIT1
REVEL	0.549	indeterminate
SaProt	LLR -13.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 6,702 bp · p 0.49 · regional, not allelic
Overall
CADD	27.9	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

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: KRIT1
Protein: p.Arg16Pro
Coding: c.47G>C
MANE Select: NM_194454
dbSNP: rs1313893193
Type: single nucleotide variant
Location: chr7:92242089 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 16: a β-strand; the 'n-terminal domain similar to nudix hydrolase domain' region

Full KRIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebral cavernous malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRIT1 p.Arg16Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
KRIT1 c.1146+1G>A Pathogenic ★★ same condition
KRIT1 c.1146+1G>T Pathogenic ★★ same condition
KRIT1 c.1147-13C>G Pathogenic ★★ same condition
KRIT1 c.1147-2A>G Pathogenic/Likely pathogenic ★★ same condition
KRIT1 c.1255-1G>A Pathogenic ★★ same condition
KRIT1 c.1255-2A>G Pathogenic ★★ same condition
KRIT1 c.1412-2A>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/krit1-p-arg16pro (accessed [today's date]).

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