Is EMC1 p.Arg802Cys (c.2404C>T) pathogenic?

EMC1 p.Arg802Cys (c.2404C>T) is classified Uncertain significance in EMC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). AlphaMissense: likely pathogenic (0.9483); Ultra-rare (popmax 0.0201%, eas); Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.Arg802Cys (c.2404C>T)?

EMC1 p.Arg802Cys (c.2404C>T) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is EMC1 p.Arg802Cys (c.2404C>T) in the general population?

EMC1 p.Arg802Cys (c.2404C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Arg802Cys (c.2404C>T)?

AlphaMissense predicts likely pathogenic (score 0.9483) — an in-silico prediction, not a clinical call.

EMC1 p.Arg802Cys

c.2404C>T · rs372151221 · VCV1345905

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9483 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9483	likely pathogenic
REVEL	0.51	indeterminate
SaProt	LLR -13.04	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.0201% East Asian · 9/44,824 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00236% 38/1,612,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,980
African / African-American	0.0187%	5,350
South Asian	0.0044%	22,738
Admixed American	0.00167%	59,908
Remaining individualsnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)	0.000763%	130,988

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EMC1
Protein: p.Arg802Cys
Coding: c.2404C>T
MANE Select: NM_015047
dbSNP: rs372151221
Type: single nucleotide variant
Location: chr1:19222807 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 802: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

Similar variants

EMC1 p.Arg802His Uncertain significance ★★ ⚠ same residue
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same condition
EMC1 p.Thr82Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
EMC1 c.1782+3G>A Uncertain significance ★★ same condition
EMC1 c.509+6G>A Uncertain significance ★★ same condition
EMC1 p.Ala152Val Uncertain significance ★★ ⚠ same condition
EMC1 p.Ala21Thr Uncertain significance ★★ ⚠ same condition
EMC1 p.Ala43Val Uncertain significance ★★ ⚠ 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-p-arg802cys (accessed [today's date]).

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