Is EML2 p.Met32Arg (c.95T>G) pathogenic?

EML2 p.Met32Arg (c.95T>G) is classified Uncertain significance in EML2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.9708); Ultra-rare (popmax 0.0165%, mid).

How common is EML2 p.Met32Arg (c.95T>G) in the general population?

EML2 p.Met32Arg (c.95T>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about EML2 p.Met32Arg (c.95T>G)?

AlphaMissense predicts likely pathogenic (score 0.9708) — an in-silico prediction, not a clinical call.

EML2 p.Met32Arg

c.95T>G · rs768343736 · VCV3088660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9708	likely pathogenic
REVEL	0.47	indeterminate
SaProt	LLR -14.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	gain · loss 0.07 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.2 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000205% 3/1,461,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.00223%	44,874
European (non-Finnish)	8.47e-05%	1,180,027

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: EML2
Protein: p.Met32Arg
Coding: c.95T>G
MANE Select: NM_012155
dbSNP: rs768343736
Type: single nucleotide variant
Location: chr19:45638589 (GRCh38)
Gene constraint: LOEUF 0.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.78 · 1 PDB
Residue 32: the 'tandem atypical propeller in emls' region; an α-helix

Full EML2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EML2 p.Ala121Val Uncertain significance ★ ⚠ same type
EML2 p.Ala207Ser Uncertain significance ★ ⚠ same type
EML2 p.Ala288Val Uncertain significance ★ ⚠ same type
EML2 p.Ala302Thr Uncertain significance ★ ⚠ same type
EML2 p.Ala384Val Uncertain significance ★ ⚠ same type
EML2 p.Ala473Pro Uncertain significance ★ ⚠ same type
EML2 p.Ala546Thr Uncertain significance ★ ⚠ same type
EML2 p.Ala571Val 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/eml2-p-met32arg (accessed [today's date]).

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