Is EFEMP2 p.Cys177= (c.531C>T) pathogenic?

EFEMP2 p.Cys177= (c.531C>T) is classified Likely benign in EFEMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-26). Ultra-rare (popmax 0.0187%, afr); Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with EFEMP2 p.Cys177= (c.531C>T)?

EFEMP2 p.Cys177= (c.531C>T) is associated with cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is EFEMP2 p.Cys177= (c.531C>T) in the general population?

EFEMP2 p.Cys177= (c.531C>T) is ultra-rare (popmax 0.0187%, 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.Cys177=

c.531C>T · rs762305922 · VCV774041

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, 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 -5.5	GERP -3.7
Overall
CADD	8.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/75,032 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.00204% 33/1,613,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,359
European (non-Finnish)	0.00161%	62,106

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.Cys177=
Coding: c.531C>T
MANE Select: NM_016938
dbSNP: rs762305922
Type: single nucleotide variant
Location: chr11:65870197 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB
Residue 177: 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

For Autosomal recessive cutis laxa type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
EFEMP2 p.Ala103Thr 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-cys177 (accessed [today's date]).

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