Is EML5 p.Phe1950Leu (c.5848T>C) pathogenic?

EML5 p.Phe1950Leu (c.5848T>C) is classified Uncertain significance in EML5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.9887); Absent from gnomAD v4.1.

How common is EML5 p.Phe1950Leu (c.5848T>C) in the general population?

EML5 p.Phe1950Leu (c.5848T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EML5 p.Phe1950Leu (c.5848T>C)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

EML5 p.Phe1950Leu

c.5848T>C · VCV4017854

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic · top 9% in EML5
REVEL	0.395	indeterminate
SaProt	LLR -10.70	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.34	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 414 bp · p 0.9 · regional, not allelic
Overall
CADD	24.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F1942L vs ClinVar F1950L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EML5
Protein: p.Phe1950Leu
Coding: c.5848T>C
MANE Select: NM_183387
Type: single nucleotide variant
Location: chr14:88616191 (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-phe1950leu (accessed [today's date]).

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