Is MECOM p.Asp128= (c.384C>T) pathogenic?

MECOM p.Asp128= (c.384C>T) is classified Benign/Likely benign in MECOM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-02). Low-frequency (popmax 2.17%, amr); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Asp128= (c.384C>T)?

MECOM p.Asp128= (c.384C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Asp128= (c.384C>T) in the general population?

MECOM p.Asp128= (c.384C>T) is low-frequency (popmax 2.17%, amr) (gnomAD).

MECOM p.Asp128=

c.384C>T · VCV3394235

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.17%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -2.3, phastCons 1
Overall
CADD	9.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.17% Admixed American · 1,272/58,656 alleles

Filtering AF 2.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.03%

Overall 0.0926% 1,486/1,604,482 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.17%	46
East Asian	0.151%	663
Remaining individualsnot grpmax-eligible	0.103%	970
African / African-American	0.0817%	1,224
Middle Eastern	0.0166%	6,032
European (non-Finnish)	0.00179%	55,967

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: MECOM
Protein: p.Asp128=
Coding: c.384C>T
MANE Select: NM_004991
Type: single nucleotide variant
Location: chr3:169143824 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 128: the set domain

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.Asp128Glu Uncertain significance ★ ⚠ same residue
MECOM p.Asp128Gly Uncertain significance ★ ⚠ same residue
MECOM p.Asp128His 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-asp128 (accessed [today's date]).

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