Is EFEMP2 p.Pro190= (c.570G>A) pathogenic?

EFEMP2 p.Pro190= (c.570G>A) is classified Benign/Likely benign in EFEMP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.14%, afr); Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with EFEMP2 p.Pro190= (c.570G>A)?

EFEMP2 p.Pro190= (c.570G>A) is associated with cutis laxa, autosomal recessive, type 1B, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is EFEMP2 p.Pro190= (c.570G>A) in the general population?

EFEMP2 p.Pro190= (c.570G>A) is rare (popmax 0.14%, afr) (gnomAD).

How is Autosomal recessive cutis laxa type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EFEMP2 p.Pro190=

c.570G>A · rs145853251 · VCV472829

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.14%, afr)

Conditions

cutis laxa, autosomal recessive, type 1B

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 -20	GERP -3.7
Overall
CADD	0.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% African / African-American · 105/75,034 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.00898% 145/1,613,840 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.14%	715
Admixed American	0.0283%	3,531
Remaining individualsnot grpmax-eligible	0.0192%	5,208
South Asian	0.0022%	45,539
European (non-Finnish)	0.000763%	131,112

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: EFEMP2
Protein: p.Pro190=
Coding: c.570G>A
MANE Select: NM_016938
dbSNP: rs145853251
Type: single nucleotide variant
Location: chr11:65870158 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB
Residue 190: a disulfide bond; the egf-like 3; calcium-binding domain

Full EFEMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cutis laxa, autosomal recessive, type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

For Autosomal recessive cutis laxa type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

EFEMP2 p.Pro190Leu Uncertain significance ★ ⚠ same residue
EFEMP2 p.Arg279Cys Likely pathogenic ★★ same condition
EFEMP2 p.Asp203Ala Pathogenic/Likely pathogenic ★★ same condition
EFEMP2 p.Glu126Lys Pathogenic/Likely pathogenic ★★ same condition
EFEMP2 p.Glu161Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
EFEMP2 p.Glu167Ter Pathogenic ★★ same condition
EFEMP2 c.161-6C>G Uncertain significance ★★ same condition
EFEMP2 c.491-5C>G 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/efemp2-p-pro190 (accessed [today's date]).

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