Is EML6 p.Ala6Val (c.17C>T) pathogenic?

EML6 p.Ala6Val (c.17C>T) is classified Uncertain significance in EML6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.4679); Very rare (popmax 0.00158%, nfe).

How common is EML6 p.Ala6Val (c.17C>T) in the general population?

EML6 p.Ala6Val (c.17C>T) is very rare (popmax 0.00158%, nfe) (gnomAD).

What do computational predictors say about EML6 p.Ala6Val (c.17C>T)?

AlphaMissense predicts ambiguous (score 0.4679) — an in-silico prediction, not a clinical call.

EML6 p.Ala6Val

c.17C>T · rs2549606181 · VCV2240147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00158%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4679	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -4.21	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 245 kb · p 7.8e-23 · regional, not allelic
Overall
CADD	26.9	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

Grpmax group 0.00158% European (non-Finnish) · 18/1,137,162 alleles

Filtering AF 0.000989% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000816%

Overall 0.00131% 18/1,375,300 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: EML6
Protein: p.Ala6Val
Coding: c.17C>T
MANE Select: NM_001039753
dbSNP: rs2549606181
Type: single nucleotide variant
Location: chr2:54725078 (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.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
EML6 p.Ala1014Thr 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/eml6-p-ala6val (accessed [today's date]).

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