Is EMC7 p.Phe8Leu (c.24C>G) pathogenic?

EMC7 p.Phe8Leu (c.24C>G) is classified Uncertain significance in EMC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.2593); Absent from gnomAD v4.1.

How common is EMC7 p.Phe8Leu (c.24C>G) in the general population?

EMC7 p.Phe8Leu (c.24C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EMC7 p.Phe8Leu (c.24C>G)?

AlphaMissense predicts likely benign (score 0.2593) — an in-silico prediction, not a clinical call.

EMC7 p.Phe8Leu

c.24C>G · VCV3508157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2593 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2593	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -4.93	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 0.68	GERP -2.4, phastCons 0.001
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 0.11 · regional, not allelic
Overall
CADD	7.44	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: EMC7
Protein: p.Phe8Leu
Coding: c.24C>G
MANE Select: NM_020154
Type: single nucleotide variant
Location: chr15:34101816 (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.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.Asp43Asn Uncertain significance ★ ⚠ same type
EMC7 p.Asp43His 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-phe8leu (accessed [today's date]).

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