Is EMP2 p.Phe7Leu (c.21C>G) pathogenic?

EMP2 p.Phe7Leu (c.21C>G) is classified Pathogenic in EMP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-06-05). AlphaMissense: likely pathogenic (0.7135); Absent from gnomAD v4.1; Associated with nephrotic syndrome, type 10.

What condition is associated with EMP2 p.Phe7Leu (c.21C>G)?

EMP2 p.Phe7Leu (c.21C>G) is associated with nephrotic syndrome, type 10 (ClinVar).

How common is EMP2 p.Phe7Leu (c.21C>G) in the general population?

EMP2 p.Phe7Leu (c.21C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMP2 p.Phe7Leu (c.21C>G)?

AlphaMissense predicts likely pathogenic (score 0.7135) — an in-silico prediction, not a clinical call.

EMP2 p.Phe7Leu

Q: How is Hereditary steroid-resistant nephrotic syndrome inherited?

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

c.21C>G · rs730882194 · VCV139532

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome, type 10

Computational evidence

Protein change
AlphaMissense	0.7135	likely pathogenic ✓ concordant with ClinVar
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -0.068, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 15 kb · p 0.029 · regional, not allelic
Overall
CADD	21.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EMP2
Protein: p.Phe7Leu
Coding: c.21C>G
MANE Select: NM_001424
dbSNP: rs730882194
Type: single nucleotide variant
Location: chr16:10547597 (GRCh38)
Gene constraint: LOEUF 1.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.89
Residue 7: a UniProt-annotated variant site (in nphs10; decreased amount of cav1)

Full EMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrotic syndrome, type 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary steroid-resistant nephrotic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal

Similar variants

EMP2 p.Ala63Val Uncertain significance ★★ ⚠ same condition
EMP2 p.Arg166His Uncertain significance ★★ ⚠ same condition
EMP2 p.Tyr143His Uncertain significance ★★ ⚠ same condition
EMP2 c.170-14C>T Benign ★★ same condition
EMP2 c.78+1G>C Likely pathogenic ★ same condition
EMP2 p.Ala10Thr Uncertain significance ★ ⚠ same condition
EMP2 p.Gln62Ter Uncertain significance ★ same condition
EMP2 p.Trp29_Val30delinsTer Likely 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/emp2-p-phe7leu (accessed [today's date]).

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