Is EMC1 p.Asp239His (c.715G>C) pathogenic?

EMC1 p.Asp239His (c.715G>C) is classified Uncertain significance in EMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-22). AlphaMissense: likely benign (0.264); Very rare (popmax 0.000339%, nfe).

How common is EMC1 p.Asp239His (c.715G>C) in the general population?

EMC1 p.Asp239His (c.715G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about EMC1 p.Asp239His (c.715G>C)?

AlphaMissense predicts likely benign (score 0.264) — an in-silico prediction, not a clinical call.

EMC1 p.Asp239His

c.715G>C · VCV4775815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.264	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic
Overall
CADD	26.1	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 0.000339% European (non-Finnish) · 4/1,180,026 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,874 alleles · very 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.Asp239His
Coding: c.715G>C
MANE Select: NM_015047
Type: single nucleotide variant
Location: chr1:19240368 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 10 PDB
Residue 239: a β-strand

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

Similar variants

EMC1 p.Asp239Glu Uncertain significance ★★ ⚠ same residue
EMC1 c.287-1G>A Likely pathogenic ★★ same type
EMC1 c.787-1G>A Likely pathogenic ★★ same type
EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg687Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same type
EMC1 p.Arg908Ter Pathogenic ★★ same type

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-asp239his (accessed [today's date]).

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