Is EML3 p.Pro50Ser (c.148C>T) pathogenic?

EML3 p.Pro50Ser (c.148C>T) is classified Uncertain significance in EML3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0616); Absent from gnomAD v4.1.

How common is EML3 p.Pro50Ser (c.148C>T) in the general population?

EML3 p.Pro50Ser (c.148C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EML3 p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

EML3 p.Pro50Ser

c.148C>T · VCV4248769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -3.3, phastCons 0.12
Regional constraint	o/e 1.01	unconstrained · MANE · 2,120 bp · p 0.81 · regional, not allelic
Overall
CADD	5.297	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

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: EML3
Protein: p.Pro50Ser
Coding: c.148C>T
MANE Select: NM_153265
Type: single nucleotide variant
Location: chr11:62611471 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.62
Residue 50: the 'disordered' region

Full EML3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EML3 p.Ala178Ser Uncertain significance ★ ⚠ same type
EML3 p.Ala366Val Uncertain significance ★ same type
EML3 p.Ala38Val Uncertain significance ★ ⚠ same type
EML3 p.Ala512Ser Uncertain significance ★ ⚠ same type
EML3 p.Ala875Thr Uncertain significance ★ ⚠ same type
EML3 p.Arg141Gly Uncertain significance ★ ⚠ same type
EML3 p.Arg165Gln Uncertain significance ★ ⚠ same type
EML3 p.Arg165Trp 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/eml3-p-pro50ser (accessed [today's date]).

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