Is EMP2 p.Arg88Cys (c.262C>T) pathogenic?

EMP2 p.Arg88Cys (c.262C>T) is classified Uncertain significance in EMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.5543); Ultra-rare (popmax 0.0329%, mid).

How common is EMP2 p.Arg88Cys (c.262C>T) in the general population?

EMP2 p.Arg88Cys (c.262C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about EMP2 p.Arg88Cys (c.262C>T)?

AlphaMissense predicts ambiguous (score 0.5543) — an in-silico prediction, not a clinical call.

EMP2 p.Arg88Cys

c.262C>T · rs780343624 · VCV2214763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5543 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Computational evidence

Protein change
AlphaMissense	0.5543	ambiguous
REVEL	0.621	indeterminate
SaProt	LLR -7.65	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP -1.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 15 kb · p 0.029 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00186% 30/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.0143%	7,006
East Asian	0.00223%	44,876
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.0011%	90,770

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: EMP2
Protein: p.Arg88Cys
Coding: c.262C>T
MANE Select: NM_001424
dbSNP: rs780343624
Type: single nucleotide variant
Location: chr16:10537982 (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.Arg88Leu Uncertain significance ★ ⚠ same residue
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

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-arg88cys (accessed [today's date]).

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