Is EML2 p.Ala384Val (c.1151C>T) pathogenic?

EML2 p.Ala384Val (c.1151C>T) is classified Uncertain significance in EML2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely benign (0.3321); Ultra-rare (popmax 0.0991%, sas).

How common is EML2 p.Ala384Val (c.1151C>T) in the general population?

EML2 p.Ala384Val (c.1151C>T) is ultra-rare (popmax 0.0991%, sas) (gnomAD).

What do computational predictors say about EML2 p.Ala384Val (c.1151C>T)?

AlphaMissense predicts likely benign (score 0.3321) — an in-silico prediction, not a clinical call.

EML2 p.Ala384Val

c.1151C>T · rs768839937 · VCV2594607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3321 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0991%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3321	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -0.71, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.2 · regional, not allelic
Overall
CADD	26.5	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 0.0991% South Asian · 90/90,858 alleles

Filtering AF 0.0825% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.00577% 93/1,611,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0991%	1,010
Remaining individualsnot grpmax-eligible	0.00321%	31,151
European (non-Finnish)	8.48e-05%	1,179,473

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.Ala384Val
Coding: c.1151C>T
MANE Select: NM_012155
dbSNP: rs768839937
Type: single nucleotide variant
Location: chr19:45619163 (GRCh38)
Gene constraint: LOEUF 0.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.78 · 1 PDB
Residue 384: the 'tandem atypical propeller in emls' region

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.Ala473Pro Uncertain significance ★ ⚠ same type
EML2 p.Ala546Thr Uncertain significance ★ ⚠ same type
EML2 p.Ala571Val Uncertain significance ★ ⚠ same type
EML2 p.Ala609Asp 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-ala384val (accessed [today's date]).

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