Is EMC1 p.Pro585Gln (c.1754C>A) pathogenic?

EMC1 p.Pro585Gln (c.1754C>A) is classified Likely pathogenic in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: likely pathogenic (0.9916); Absent from gnomAD v4.1; Associated with cerebellar atrophy, visual impairment, and psychomotor retardation;.

What condition is associated with EMC1 p.Pro585Gln (c.1754C>A)?

EMC1 p.Pro585Gln (c.1754C>A) is associated with cerebellar atrophy, visual impairment, and psychomotor retardation; (ClinVar).

How common is EMC1 p.Pro585Gln (c.1754C>A) in the general population?

EMC1 p.Pro585Gln (c.1754C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC1 p.Pro585Gln (c.1754C>A)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

EMC1 p.Pro585Gln

c.1754C>A · rs1572001567 · VCV801454

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cerebellar atrophy, visual impairment, and psychomotor retardation;

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic ✓ concordant with ClinVar
REVEL	0.416	indeterminate
SaProt	LLR -15.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	29.3	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: EMC1
Protein: p.Pro585Gln
Coding: c.1754C>A
dbSNP: rs1572001567
Type: single nucleotide variant
Location: chr1:19232652 (GRCh38)

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

Disease context

cerebellar atrophy, visual impairment, and psychomotor retardation; — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro585gln (accessed [today's date]).

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