Is KRIT1 p.Val660= (c.1980A>G) pathogenic?

KRIT1 p.Val660= (c.1980A>G) is classified Benign in KRIT1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-01). Common (popmax 34.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with angiokeratoma corporis diffusum with arteriovenous fistulas.

KRIT1 p.Val660=

Q: What condition is associated with KRIT1 p.Val660= (c.1980A>G)?

KRIT1 p.Val660= (c.1980A>G) is associated with angiokeratoma corporis diffusum with arteriovenous fistulas, cerebral cavernous malformation (ClinVar).

Q: How common is KRIT1 p.Val660= (c.1980A>G) in the general population?

KRIT1 p.Val660= (c.1980A>G) is common (popmax 34.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1980A>G · rs11542682 · VCV263098

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 34.6%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

angiokeratoma corporis diffusum with arteriovenous fistulas

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -0.047, phastCons 0.76
Overall
CADD	5.517	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 34.6% East Asian · 15,513/44,802 alleles

Filtering AF 34.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 34%

Overall 10.2% 164,232/1,612,268 alleles · common exomes 146,928/1,460,140 · genomes 17,304/152,128 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	34.6%	3
South Asian	16.3%	6
Amishnot grpmax-eligible	14.1%	7
African / African-American	12.7%	8
Remaining individualsnot grpmax-eligible	11%	9
Middle Eastern	11%	9
Admixed American	10.5%	9
Ashkenazi Jewishnot grpmax-eligible	10.1%	10
Finnishnot grpmax-eligible	8.67%	12
European (non-Finnish)	8.64%	12

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.Val660=
Coding: c.1980A>G
MANE Select: NM_194454
dbSNP: rs11542682
Type: single nucleotide variant
Location: chr7:92213240 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.01 · 15 PDB
Residue 660: the ferm domain; a β-strand

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

Disease context

angiokeratoma corporis diffusum with arteriovenous fistulas — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cerebral cavernous malformation

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-val660 (accessed [today's date]).

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