Is EMC1 p.His294Pro (c.881A>C) pathogenic?

EMC1 p.His294Pro (c.881A>C) is classified Uncertain significance in EMC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1313); Ultra-rare (popmax 0.0133%, amr); Associated with Inborn genetic diseases.

What condition is associated with EMC1 p.His294Pro (c.881A>C)?

EMC1 p.His294Pro (c.881A>C) is associated with Inborn genetic diseases (ClinVar).

How common is EMC1 p.His294Pro (c.881A>C) in the general population?

EMC1 p.His294Pro (c.881A>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about EMC1 p.His294Pro (c.881A>C)?

AlphaMissense predicts likely benign (score 0.1313) — an in-silico prediction, not a clinical call.

EMC1 p.His294Pro

c.881A>C · rs772900959 · VCV1059693

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1313 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1313	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	22.8	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

Grpmax group 0.0133% Admixed American · 8/59,996 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000682% 11/1,613,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,500
European (non-Finnish)	0.000254%	393,340

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.His294Pro
Coding: c.881A>C
dbSNP: rs772900959
Type: single nucleotide variant
Location: chr1:19239891 (GRCh38)

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

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-his294pro (accessed [today's date]).

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