Is MEGF8 p.Gln2003= (c.6009G>A) pathogenic?

MEGF8 p.Gln2003= (c.6009G>A) is classified Likely benign in MEGF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Absent from gnomAD v4.1; Associated with MEGF8-related Carpenter syndrome.

What condition is associated with MEGF8 p.Gln2003= (c.6009G>A)?

MEGF8 p.Gln2003= (c.6009G>A) is associated with MEGF8-related Carpenter syndrome (ClinVar).

How common is MEGF8 p.Gln2003= (c.6009G>A) in the general population?

MEGF8 p.Gln2003= (c.6009G>A) is absent from gnomAD v4.1 (gnomAD).

MEGF8 p.Gln2003=

c.6009G>A · VCV4810779

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MEGF8-related Carpenter syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.3	phastCons 1
Overall
CADD	7.985	PHRED · no single calibrated threshold — expert panels disagree

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: MEGF8
Protein: p.Gln2003=
Coding: c.6009G>A
MANE Select: NM_001271938
Type: single nucleotide variant
Location: chr19:42362548 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)

Full MEGF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MEGF8-related Carpenter syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MEGF8 p.Arg419Ter Pathogenic/Likely pathogenic ★★ same condition
MEGF8 p.Arg991Ter Pathogenic/Likely pathogenic ★★ same condition
MEGF8 p.Ala1472Val Uncertain significance ★★ ⚠ same condition
MEGF8 p.Ala1572Thr Uncertain significance ★★ ⚠ same condition
MEGF8 p.Ala176Gly Uncertain significance ★★ ⚠ same condition
MEGF8 p.Ala1791Ser Uncertain significance ★★ same condition
MEGF8 p.Ala2104Ser Uncertain significance ★★ ⚠ same condition
MEGF8 p.Ala2349Gly 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/megf8-p-gln2003 (accessed [today's date]).

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