Is EMC6 p.Pro83Ala (c.247C>G) pathogenic?

EMC6 p.Pro83Ala (c.247C>G) is classified Uncertain significance in EMC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely benign (0.0693); Absent from gnomAD v4.1.

How common is EMC6 p.Pro83Ala (c.247C>G) in the general population?

EMC6 p.Pro83Ala (c.247C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC6 p.Pro83Ala (c.247C>G)?

AlphaMissense predicts likely benign (score 0.0693) — an in-silico prediction, not a clinical call.

EMC6 p.Pro83Ala

c.247C>G · VCV3275271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0693 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0693	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -3.30	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 329 bp · p 0.007 · regional, not allelic
Overall
CADD	18.36	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: EMC6
Protein: p.Pro83Ala
Coding: c.247C>G
MANE Select: NM_031298
Type: single nucleotide variant
Location: chr17:3669393 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 82.32 · 10 PDB
Residue 83: an α-helix

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

Similar variants

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
EMC6 p.Phe99Leu 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-pro83ala (accessed [today's date]).

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