Is EFEMP2 p.Pro47Ser (c.139C>T) pathogenic?

EFEMP2 p.Pro47Ser (c.139C>T) is classified Likely benign in EFEMP2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0875); Rare (popmax 0.117%, mid); Associated with Cardiovascular phenotype.

What condition is associated with EFEMP2 p.Pro47Ser (c.139C>T)?

EFEMP2 p.Pro47Ser (c.139C>T) is associated with Cardiovascular phenotype, cutis laxa, autosomal recessive, type 1B (ClinVar).

How common is EFEMP2 p.Pro47Ser (c.139C>T) in the general population?

EFEMP2 p.Pro47Ser (c.139C>T) is rare (popmax 0.117%, mid) (gnomAD).

What do computational predictors say about EFEMP2 p.Pro47Ser (c.139C>T)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

EFEMP2 p.Pro47Ser

c.139C>T · rs144320036 · VCV390442

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.117%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.56, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 5,433 bp · p 3.8e-05 · regional, not allelic
Overall
CADD	18.41	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% Middle Eastern · 7/5,990 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.0973% 1,510/1,551,586 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.117%	856
European (non-Finnish)	0.113%	882
Remaining individualsnot grpmax-eligible	0.105%	954
Admixed American	0.1%	1,000
South Asian	0.0607%	1,648
Ashkenazi Jewishnot grpmax-eligible	0.0558%	1,791
Finnishnot grpmax-eligible	0.0234%	4,275
African / African-American	0.0109%	9,138

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.Pro47Ser
Coding: c.139C>T
MANE Select: NM_016938
dbSNP: rs144320036
Type: single nucleotide variant
Location: chr11:65871991 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.62 (gnomAD)
Structure: AlphaFold pLDDT 82.95 · 1 PDB
Residue 47: the egf-like 1; atypical domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cutis laxa, autosomal recessive, type 1B

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 c.608-3C>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-pro47ser (accessed [today's date]).

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