Is EMP2 p.Ile51Val (c.151A>G) pathogenic?

EMP2 p.Ile51Val (c.151A>G) is classified Benign/Likely benign in EMP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1185); Low-frequency (popmax 3.03%, afr).

How common is EMP2 p.Ile51Val (c.151A>G) in the general population?

EMP2 p.Ile51Val (c.151A>G) is low-frequency (popmax 3.03%, afr) (gnomAD).

What do computational predictors say about EMP2 p.Ile51Val (c.151A>G)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

EMP2 p.Ile51Val

c.151A>G · rs73503834 · VCV1220016

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.03%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -6.24	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 1.9	GERP -0.56, phastCons 0.99
Regional constraint	o/e 1.15	unconstrained · MANE · 15 kb · p 0.029 · regional, not allelic
Overall
CADD	3.965	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 3.03% African / African-American · 2,271/75,070 alleles

Filtering AF 2.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.88%

Overall 0.174% 2,808/1,614,250 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.03%	33
Admixed American	0.268%	373
Remaining individualsnot grpmax-eligible	0.251%	398
Middle Eastern	0.231%	433
European (non-Finnish)	0.0169%	5,900
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
South Asian	0.00329%	30,362

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.Ile51Val
Coding: c.151A>G
MANE Select: NM_001424
dbSNP: rs73503834
Type: single nucleotide variant
Location: chr16:10543588 (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-ile51val (accessed [today's date]).

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