Is EMC1 p.Lys52Arg (c.155A>G) pathogenic?

EMC1 p.Lys52Arg (c.155A>G) is classified Conflicting classifications of pathogenicity in EMC1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-11). AlphaMissense: likely benign (0.0791); Rare (popmax 0.107%, eas); Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.Lys52Arg (c.155A>G)?

EMC1 p.Lys52Arg (c.155A>G) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is EMC1 p.Lys52Arg (c.155A>G) in the general population?

EMC1 p.Lys52Arg (c.155A>G) is rare (popmax 0.107%, eas) (gnomAD).

What do computational predictors say about EMC1 p.Lys52Arg (c.155A>G)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

EMC1 p.Lys52Arg

c.155A>G · rs201537299 · VCV2102121

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	21.6	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

Grpmax group 0.107% East Asian · 48/44,870 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.00297% 48/1,614,002 alleles · rare

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.Lys52Arg
Coding: c.155A>G
MANE Select: NM_015047
dbSNP: rs201537299
Type: single nucleotide variant
Location: chr1:19244971 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 52: 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.Lys52Asn Uncertain significance ★ ⚠ same residue
EMC1 p.Lys52Glu 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

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-lys52arg (accessed [today's date]).

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