Is EMP2 p.Arg120His (c.359G>A) pathogenic?

EMP2 p.Arg120His (c.359G>A) is classified Uncertain significance in EMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-22). AlphaMissense: likely benign (0.1557); Very rare (popmax 0.00937%, afr).

How common is EMP2 p.Arg120His (c.359G>A) in the general population?

EMP2 p.Arg120His (c.359G>A) is very rare (popmax 0.00937%, afr) (gnomAD).

What do computational predictors say about EMP2 p.Arg120His (c.359G>A)?

AlphaMissense predicts likely benign (score 0.1557) — an in-silico prediction, not a clinical call.

EMP2 p.Arg120His

c.359G>A · rs370673124 · VCV2140842

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00937%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1557	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -4.29	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 1.1	GERP -0.2, phastCons 0.54
Regional constraint	o/e 1.15	unconstrained · MANE · 15 kb · p 0.029 · regional, not allelic
Overall
CADD	16.57	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00937% African / African-American · 7/74,688 alleles

Filtering AF 0.00759% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00707%

Overall 0.00715% 115/1,608,686 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00937%	10,670
European (non-Finnish)	0.009%	11,109
Remaining individualsnot grpmax-eligible	0.00161%	62,302
South Asian	0.00111%	89,904

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.Arg120His
Coding: c.359G>A
MANE Select: NM_001424
dbSNP: rs370673124
Type: single nucleotide variant
Location: chr16:10533050 (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.Arg120Cys Uncertain significance ★ ⚠ same residue
EMP2 p.Ala63Val Uncertain significance ★★ ⚠ same type
EMP2 p.Ala78Thr 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-arg120his (accessed [today's date]).

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