Is EMC1 c.2802+2T>C pathogenic?

EMC1 c.2802+2T>C is classified Likely pathogenic in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). Absent from gnomAD v4.1; Associated with cerebellar atrophy, visual impairment, and psychomotor retardation;.

What condition is associated with EMC1 c.2802+2T>C?

EMC1 c.2802+2T>C is associated with cerebellar atrophy, visual impairment, and psychomotor retardation; (ClinVar).

How common is EMC1 c.2802+2T>C in the general population?

EMC1 c.2802+2T>C is absent from gnomAD v4.1 (gnomAD).

EMC1 c.2802+2T>C

rs2536637199 · VCV2626938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cerebellar atrophy, visual impairment, and psychomotor retardation;

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.94	donor loss · deltas
Pangolin	Δ0.85	loss · gain 0.47 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.3	GERP 2.3, phastCons 1
Non-coding constraint	Z 3.62	1 kb window · o/e 0.75 · regional · uncalibrated
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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
Coding: c.2802+2T>C
MANE Select: NM_015047
dbSNP: rs2536637199
Type: single nucleotide variant
Location: chr1:19219567 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB

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

Similar variants

EMC1 c.287-1G>A Likely pathogenic ★★ same condition
EMC1 c.787-1G>A Likely pathogenic ★★ same condition
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Leu266Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Met1Arg Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Thr82Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
EMC1 p.Tyr142Ter Pathogenic/Likely pathogenic ★★ same condition

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-c-2802-plus-2t-c (accessed [today's date]).

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