Is EML5 p.Thr1129= (c.3387C>A) pathogenic?

EML5 p.Thr1129= (c.3387C>A) is classified Likely benign in EML5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Very rare (popmax 0.00017%, nfe).

How common is EML5 p.Thr1129= (c.3387C>A) in the general population?

EML5 p.Thr1129= (c.3387C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

EML5 p.Thr1129=

c.3387C>A · rs746472023 · VCV2644443

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 1.4	GERP -2.1, phastCons 1
Overall
CADD	5.153	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,604 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,454,718 alleles · very rare

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: EML5
Protein: p.Thr1129=
Coding: c.3387C>A
MANE Select: NM_183387
dbSNP: rs746472023
Type: single nucleotide variant
Location: chr14:88664515 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18

Full EML5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EML5 p.Ala1787Glu Benign ★★ same type
EML5 p.Thr194Met Benign ★★ same type
EML5 p.Val1361= Benign ★★ same type
EML5 p.Ala1575Thr Uncertain significance ★ ⚠ same type
EML5 p.Ala1606Val Uncertain significance ★ ⚠ same type
EML5 p.Ala1615Val Uncertain significance ★ ⚠ same type
EML5 p.Ala1746Val Uncertain significance ★ ⚠ same type
EML5 p.Ala1787Ser 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/eml5-p-thr1129 (accessed [today's date]).

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