Is KRIT1 p.Pro291Ser (c.871C>T) pathogenic?

KRIT1 p.Pro291Ser (c.871C>T) is classified Uncertain significance in KRIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-18). AlphaMissense: likely pathogenic (0.9006); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRIT1 p.Pro291Ser (c.871C>T)?

KRIT1 p.Pro291Ser (c.871C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRIT1 p.Pro291Ser (c.871C>T) in the general population?

KRIT1 p.Pro291Ser (c.871C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRIT1 p.Pro291Ser (c.871C>T)?

AlphaMissense predicts likely pathogenic (score 0.9006) — an in-silico prediction, not a clinical call.

KRIT1 p.Pro291Ser

c.871C>T · rs2536005424 · VCV2229666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9006 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9006	likely pathogenic
REVEL	0.723	pathogenic-leaning
SaProt	LLR -11.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 3.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 34 kb · p 0.00022 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: KRIT1
Protein: p.Pro291Ser
Coding: c.871C>T
MANE Select: NM_194454
dbSNP: rs2536005424
Type: single nucleotide variant
Location: chr7:92234567 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 291: an α-helix

Full KRIT1 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

KRIT1 c.2025+3A>G Uncertain significance ★★ same condition
KRIT1 p.Arg167Cys Uncertain significance ★★ ⚠ same condition
KRIT1 p.Arg167His Uncertain significance ★★ ⚠ same condition
KRIT1 p.Arg179Gln Uncertain significance ★★ ⚠ same condition
KRIT1 p.Arg243Trp Uncertain significance ★★ ⚠ same condition
KRIT1 p.Arg306His Uncertain significance ★★ ⚠ same condition
KRIT1 p.Arg485Cys Uncertain significance ★★ ⚠ same condition
KRIT1 p.Asn403Ser 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/krit1-p-pro291ser (accessed [today's date]).

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