Is MECOM p.Asp269= (c.807C>T) pathogenic?

MECOM p.Asp269= (c.807C>T) is classified Likely benign in MECOM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Asp269= (c.807C>T)?

MECOM p.Asp269= (c.807C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Asp269= (c.807C>T) in the general population?

MECOM p.Asp269= (c.807C>T) is absent from gnomAD v4.1 (gnomAD).

MECOM p.Asp269=

c.807C>T · VCV4053313

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Overall
CADD	13.0	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: MECOM
Protein: p.Asp269=
Coding: c.807C>T
MANE Select: NM_004991
Type: single nucleotide variant
Location: chr3:169127867 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 269: the 'interaction with mapk9, smad3 and probably suv39h1' region

Full MECOM 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

Similar variants

MECOM p.Asp269Asn Uncertain significance ★★ ⚠ same residue
MECOM p.Asp269Glu Uncertain significance ★ ⚠ same residue
MECOM p.Asp269Val Uncertain significance ★ same residue
MECOM p.Ala1022Gly Uncertain significance ★★ ⚠ same condition
MECOM p.Ala1228Val Uncertain significance ★★ ⚠ same condition
MECOM p.Ala222Val Uncertain significance ★★ ⚠ same condition
MECOM p.Ala434Val Uncertain significance ★★ ⚠ same condition
MECOM p.Ala477Gly 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/mecom-p-asp269 (accessed [today's date]).

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