Is EMC1 p.Ala333Ser (c.997G>T) pathogenic?

EMC1 p.Ala333Ser (c.997G>T) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.2715); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.Ala333Ser (c.997G>T)?

EMC1 p.Ala333Ser (c.997G>T) is associated with Inborn genetic diseases (ClinVar).

How common is EMC1 p.Ala333Ser (c.997G>T) in the general population?

EMC1 p.Ala333Ser (c.997G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC1 p.Ala333Ser (c.997G>T)?

AlphaMissense predicts likely benign (score 0.2715) — an in-silico prediction, not a clinical call.

EMC1 p.Ala333Ser

c.997G>T · VCV4017709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2715 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2715	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ala333Ser
Coding: c.997G>T
MANE Select: NM_015047
Type: single nucleotide variant
Location: chr1:19239260 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 333: 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

Similar variants

EMC1 p.Ala333Val Uncertain significance ★ ⚠ same residue
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
EMC1 p.Ala509Val 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-ala333ser (accessed [today's date]).

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