Is EME2 p.Ala90= (c.270C>T) pathogenic?

EME2 p.Ala90= (c.270C>T) is classified Likely benign in EME2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Rare (popmax 0.648%, mid).

How common is EME2 p.Ala90= (c.270C>T) in the general population?

EME2 p.Ala90= (c.270C>T) is rare (popmax 0.648%, mid) (gnomAD).

EME2 p.Ala90=

c.270C>T · rs199761703 · VCV2645946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.648%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -3.1
Overall
CADD	3.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.648% Middle Eastern · 29/4,474 alleles

Filtering AF 0.512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.495%

Overall 0.369% 5,721/1,549,006 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.72%	58
Middle Easterngrpmax	0.648%	154
South Asian	0.553%	181
Remaining individualsnot grpmax-eligible	0.462%	216
European (non-Finnish)	0.373%	268
Admixed American	0.202%	496
African / African-American	0.0656%	1,523
Finnishnot grpmax-eligible	0.0376%	2,658

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EME2
Protein: p.Ala90=
Coding: c.270C>T
MANE Select: NM_001257370
dbSNP: rs199761703
Type: single nucleotide variant
Location: chr16:1773727 (GRCh38)
Gene constraint: LOEUF 1.942 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.73 · 1 PDB
Residue 90: an α-helix; the 'nuclease-like domain; forms the post-nick dna binding interface and is involved in dna recognition and bending' region

Full EME2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPSB3 p.Arg90Trp Uncertain significance ★ ⚠ same residue
MRPS34 p.Gln32Ter Pathogenic/Likely pathogenic ★★ same type
MRPS34 p.Arg17Pro Uncertain significance ★★ ⚠ same type
MRPS34 p.Arg27Lys Uncertain significance ★★ ⚠ same type
MRPS34 p.Arg63His Uncertain significance ★★ ⚠ same type
MRPS34 p.Arg9Gln Uncertain significance ★★ ⚠ same type
MRPS34 p.Glu39Asp Uncertain significance ★★ ⚠ same type
MRPS34 p.Ser84Phe 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/eme2-p-ala90 (accessed [today's date]).

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