Is EMC3 p.Pro211Leu (c.632C>T) pathogenic?

EMC3 p.Pro211Leu (c.632C>T) is classified Uncertain significance in EMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely pathogenic (0.841); Absent from gnomAD v4.1.

How common is EMC3 p.Pro211Leu (c.632C>T) in the general population?

EMC3 p.Pro211Leu (c.632C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC3 p.Pro211Leu (c.632C>T)?

AlphaMissense predicts likely pathogenic (score 0.841) — an in-silico prediction, not a clinical call.

EMC3 p.Pro211Leu

c.632C>T · VCV4664033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.841	likely pathogenic
REVEL	0.669	pathogenic-leaning
SaProt	LLR -13.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 9,545 bp · p 1.7e-08 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: EMC3
Protein: p.Pro211Leu
Coding: c.632C>T
MANE Select: NM_001394674
Type: single nucleotide variant
Location: chr3:9969744 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 10 PDB

Full EMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC3 c.-242+3401G>A Uncertain significance ★ same type
EMC3 c.-242+3659C>G Uncertain significance ★ same type
EMC3 p.Ala212Thr Uncertain significance ★ ⚠ same type
EMC3 p.Arg180Trp Uncertain significance ★ ⚠ same type
EMC3 p.Arg57Gln Uncertain significance ★ ⚠ same type
EMC3 p.Arg93Trp Uncertain significance ★ ⚠ same type
EMC3 p.Asn175Ser Uncertain significance ★ ⚠ same type
EMC3 p.Asp41Asn 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/emc3-p-pro211leu (accessed [today's date]).

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