Is EMC6 p.Val19Ala (c.56T>C) pathogenic?

EMC6 p.Val19Ala (c.56T>C) is classified Uncertain significance in EMC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: ambiguous (0.4606); Absent from gnomAD v4.1.

How common is EMC6 p.Val19Ala (c.56T>C) in the general population?

EMC6 p.Val19Ala (c.56T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC6 p.Val19Ala (c.56T>C)?

AlphaMissense predicts ambiguous (score 0.4606) — an in-silico prediction, not a clinical call.

EMC6 p.Val19Ala

c.56T>C · VCV3275272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4606 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4606	ambiguous
REVEL	0.516	indeterminate
SaProt	LLR -7.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 329 bp · p 0.007 · regional, not allelic
Overall
CADD	25.9	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

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: EMC6
Protein: p.Val19Ala
Coding: c.56T>C
MANE Select: NM_031298
Type: single nucleotide variant
Location: chr17:3669202 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 10 PDB
Residue 19: an α-helix

Full EMC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC6 p.Val19Leu Uncertain significance ★ ⚠ same residue
EMC6 p.Arg20Gln Uncertain significance ★ ⚠ same type
EMC6 p.Arg72Lys Uncertain significance ★ ⚠ same type
EMC6 p.Arg8Leu Uncertain significance ★ ⚠ same type
EMC6 p.Gly42Arg Uncertain significance ★ ⚠ same type
EMC6 p.Gly92Val Uncertain significance ★ ⚠ same type
EMC6 p.Leu49Val Uncertain significance ★ ⚠ same type
EMC6 p.Leu84Phe 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/emc6-p-val19ala (accessed [today's date]).

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