Is KRIT1 p.Ser295= (c.885C>T) pathogenic?

KRIT1 p.Ser295= (c.885C>T) is classified Likely benign in KRIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-11). Ultra-rare (popmax 0.0117%, amr); Associated with cerebral cavernous malformation.

What condition is associated with KRIT1 p.Ser295= (c.885C>T)?

KRIT1 p.Ser295= (c.885C>T) is associated with cerebral cavernous malformation (ClinVar).

How common is KRIT1 p.Ser295= (c.885C>T) in the general population?

KRIT1 p.Ser295= (c.885C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

KRIT1 p.Ser295=

c.885C>T · rs761571988 · VCV1589538

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

cerebral cavernous malformation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 1.3, phastCons 1
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,988 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000806% 13/1,612,882 alleles · ultra-rare exomes 12/1,460,756 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,570
Remaining individualsnot grpmax-eligible	0.0016%	62,446
South Asian	0.0011%	91,054
European (non-Finnish)	0.000339%	294,757

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: KRIT1
Protein: p.Ser295=
Coding: c.885C>T
MANE Select: NM_194454
dbSNP: rs761571988
Type: single nucleotide variant
Location: chr7:92234553 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 295: an α-helix

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 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
KRIT1 c.1563+1G>A 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-ser295 (accessed [today's date]).

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