Is EMP2 p.Ala151Pro (c.451G>C) pathogenic?

EMP2 p.Ala151Pro (c.451G>C) is classified Uncertain significance in EMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-15). AlphaMissense: ambiguous (0.5554); Ultra-rare (popmax 0.0445%, nfe).

How common is EMP2 p.Ala151Pro (c.451G>C) in the general population?

EMP2 p.Ala151Pro (c.451G>C) is ultra-rare (popmax 0.0445%, nfe) (gnomAD).

What do computational predictors say about EMP2 p.Ala151Pro (c.451G>C)?

AlphaMissense predicts ambiguous (score 0.5554) — an in-silico prediction, not a clinical call.

EMP2 p.Ala151Pro

c.451G>C · rs143506635 · VCV2077728

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5554 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5554	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3.4, phastCons 0.6
Regional constraint	o/e 1.15	unconstrained · MANE · 15 kb · p 0.029 · regional, not allelic
Overall
CADD	14.93	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 0.0445% European (non-Finnish) · 524/1,177,168 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.0345% 554/1,608,078 alleles · ultra-rare exomes 515/1,456,010 · genomes 39/152,068 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0445%	2,247
Finnishnot grpmax-eligible	0.0173%	5,794
Remaining individualsnot grpmax-eligible	0.0161%	6,227
African / African-American	0.012%	8,316

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.Ala151Pro
Coding: c.451G>C
MANE Select: NM_001424
dbSNP: rs143506635
Type: single nucleotide variant
Location: chr16:10532958 (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-ala151pro (accessed [today's date]).

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