Is EMP3 p.Leu72Phe (c.214C>T) pathogenic?

EMP3 p.Leu72Phe (c.214C>T) is classified Uncertain significance in EMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1988); Absent from gnomAD v4.1.

How common is EMP3 p.Leu72Phe (c.214C>T) in the general population?

EMP3 p.Leu72Phe (c.214C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMP3 p.Leu72Phe (c.214C>T)?

AlphaMissense predicts likely benign (score 0.1988) — an in-silico prediction, not a clinical call.

EMP3 p.Leu72Phe

c.214C>T · VCV4017907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1988	likely benign
REVEL	0.748	pathogenic-leaning
SaProt	LLR -6.15	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,622 bp · p 0.1 · regional, not allelic
Overall
CADD	26.0	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: EMP3
Protein: p.Leu72Phe
Coding: c.214C>T
MANE Select: NM_001425
Type: single nucleotide variant
Location: chr19:48329384 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68

Full EMP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMP3 p.Ala119Val Uncertain significance ★ ⚠ same type
EMP3 p.Ala122Ser Uncertain significance ★ ⚠ same type
EMP3 p.Arg162Gln Uncertain significance ★ ⚠ same type
EMP3 p.Arg93Gln Uncertain significance ★ ⚠ same type
EMP3 p.Asn47Ser Uncertain significance ★ ⚠ same type
EMP3 p.Asp42Asn Uncertain significance ★ ⚠ same type
EMP3 p.Asp48Asn Uncertain significance ★ ⚠ same type
EMP3 p.Glu163Gln Uncertain significance ★ same type

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/emp3-p-leu72phe (accessed [today's date]).

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