Is EFEMP2 p.Pro370= (c.1110C>A) pathogenic?

EFEMP2 p.Pro370= (c.1110C>A) is classified Uncertain significance in EFEMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-05). Very rare (popmax 0.00133%, afr); Associated with cutis laxa, autosomal recessive, type 1B.

What condition is associated with EFEMP2 p.Pro370= (c.1110C>A)?

EFEMP2 p.Pro370= (c.1110C>A) is associated with cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is EFEMP2 p.Pro370= (c.1110C>A) in the general population?

EFEMP2 p.Pro370= (c.1110C>A) is very rare (popmax 0.00133%, 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.Pro370=

c.1110C>A · rs146180527 · VCV1045287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

cutis laxa, autosomal recessive, type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.84	donor gain · deltas
Pangolin	Δ0.41	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -4	GERP -3.7
Overall
CADD	18.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,934
European (non-Finnish)	0.000424%	236,009

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.Pro370=
Coding: c.1110C>A
MANE Select: NM_016938
dbSNP: rs146180527
Type: single nucleotide variant
Location: chr11:65867921 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB

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-pro370 (accessed [today's date]).

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