Is EMC7 p.Asp43His (c.127G>C) pathogenic?

EMC7 p.Asp43His (c.127G>C) is classified Uncertain significance in EMC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). AlphaMissense: ambiguous (0.5277); Absent from gnomAD v4.1.

How common is EMC7 p.Asp43His (c.127G>C) in the general population?

EMC7 p.Asp43His (c.127G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC7 p.Asp43His (c.127G>C)?

AlphaMissense predicts ambiguous (score 0.5277) — an in-silico prediction, not a clinical call.

EMC7 p.Asp43His

c.127G>C · rs770350127 · VCV2306659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5277 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5277	ambiguous
REVEL	0.394	indeterminate
SaProt	LLR -8.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	31.0	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

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: EMC7
Protein: p.Asp43His
Coding: c.127G>C
MANE Select: NM_020154
dbSNP: rs770350127
Type: single nucleotide variant
Location: chr15:34101713 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.54 · 14 PDB

Full EMC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC7 p.Asp43Asn Uncertain significance ★ ⚠ same residue
EMC7 p.Gly38= Benign ★★ same type
EMC7 p.Ala238Pro Uncertain significance ★ ⚠ same type
EMC7 p.Ala30Val Uncertain significance ★ ⚠ same type
EMC7 p.Ala31Thr Uncertain significance ★ ⚠ same type
EMC7 p.Ala4Val Uncertain significance ★ ⚠ same type
EMC7 p.Arg44His Uncertain significance ★ ⚠ same type
EMC7 p.Gly237Ala Uncertain significance ★ ⚠ 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/emc7-p-asp43his (accessed [today's date]).

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