Is EMC1 p.Ala925Pro (c.2773G>C) pathogenic?

EMC1 p.Ala925Pro (c.2773G>C) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely pathogenic (0.9935); Absent from gnomAD v4.1.

How common is EMC1 p.Ala925Pro (c.2773G>C) in the general population?

EMC1 p.Ala925Pro (c.2773G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC1 p.Ala925Pro (c.2773G>C)?

AlphaMissense predicts likely pathogenic (score 0.9935) — an in-silico prediction, not a clinical call.

EMC1 p.Ala925Pro

c.2773G>C · VCV4088046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9935	likely pathogenic · top 4% in EMC1
REVEL	0.32	indeterminate
SaProt	LLR -12.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	31.0	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: EMC1
Protein: p.Ala925Pro
Coding: c.2773G>C
MANE Select: NM_015047
Type: single nucleotide variant
Location: chr1:19219598 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 925: a β-strand

Full EMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC1 p.Ala925Thr Uncertain significance ★★ ⚠ same residue
EMC1 c.287-1G>A Likely pathogenic ★★ same type
EMC1 c.787-1G>A Likely pathogenic ★★ same type
EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg687Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg908Ter Pathogenic ★★ 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/emc1-p-ala925pro (accessed [today's date]).

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