Is EML6 p.Gln96Pro (c.287A>C) pathogenic?

EML6 p.Gln96Pro (c.287A>C) is classified Uncertain significance in EML6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely pathogenic (0.7885); Absent from gnomAD v4.1.

How common is EML6 p.Gln96Pro (c.287A>C) in the general population?

EML6 p.Gln96Pro (c.287A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EML6 p.Gln96Pro (c.287A>C)?

AlphaMissense predicts likely pathogenic (score 0.7885) — an in-silico prediction, not a clinical call.

EML6 p.Gln96Pro

c.287A>C · VCV3844751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7885 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7885	likely pathogenic
REVEL	0.214	benign-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 245 kb · p 7.8e-23 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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: EML6
Protein: p.Gln96Pro
Coding: c.287A>C
MANE Select: NM_001039753
Type: single nucleotide variant
Location: chr2:54813321 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.42

Full EML6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EML6 p.Gln96His Uncertain significance ★ ⚠ same residue
EML6 p.Arg475Gln Uncertain significance ★★ ⚠ same type
EML6 p.Gly1925Ser Uncertain significance ★★ ⚠ same type
EML6 p.Thr199Ser Uncertain significance ★★ ⚠ same type
EML6 p.Glu1412= Benign ★★ same type
EML6 p.His1237= Benign ★★ same type
EML6 p.His662= Benign ★★ same type
EML6 p.Ile220= Benign ★★ 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/eml6-p-gln96pro (accessed [today's date]).

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