Is EMP2 p.Met159Val (c.475A>G) pathogenic?

EMP2 p.Met159Val (c.475A>G) is classified Uncertain significance in EMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: ambiguous (0.5236); Absent from gnomAD v4.1.

How common is EMP2 p.Met159Val (c.475A>G) in the general population?

EMP2 p.Met159Val (c.475A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMP2 p.Met159Val (c.475A>G)?

AlphaMissense predicts ambiguous (score 0.5236) — an in-silico prediction, not a clinical call.

EMP2 p.Met159Val

c.475A>G · VCV3844772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5236 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,762)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5236	ambiguous
REVEL	0.679	pathogenic-leaning
SaProt	LLR -4.68	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.67, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 15 kb · p 0.029 · regional, not allelic
Overall
CADD	23.1	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

No allele count reported in gnomAD v4.1 (AN 1,600,762). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EMP2
Protein: p.Met159Val
Coding: c.475A>G
MANE Select: NM_001424
Type: single nucleotide variant
Location: chr16:10532934 (GRCh38)
Gene constraint: LOEUF 1.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.89

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

Similar variants

EMP2 p.Ala63Val Uncertain significance ★★ ⚠ same type
EMP2 p.Ala78Thr Uncertain significance ★★ ⚠ same type
EMP2 p.Arg120His Uncertain significance ★★ ⚠ same type
EMP2 p.Arg166His Uncertain significance ★★ ⚠ same type
EMP2 p.Glu121Lys Uncertain significance ★★ ⚠ same type
EMP2 p.Ile69Met Uncertain significance ★★ ⚠ same type
EMP2 p.Thr43Ile Uncertain significance ★★ ⚠ same type
EMP2 p.Tyr143His 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/emp2-p-met159val (accessed [today's date]).

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