Is MECOM p.Asp712Val (c.2135A>T) pathogenic?

MECOM p.Asp712Val (c.2135A>T) is classified Uncertain significance in MECOM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: likely pathogenic (0.7907); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Asp712Val (c.2135A>T)?

MECOM p.Asp712Val (c.2135A>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Asp712Val (c.2135A>T) in the general population?

MECOM p.Asp712Val (c.2135A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MECOM p.Asp712Val (c.2135A>T)?

AlphaMissense predicts likely pathogenic (score 0.7907) — an in-silico prediction, not a clinical call.

MECOM p.Asp712Val

c.2135A>T · VCV4053121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7907	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -4.21	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 14 kb · p 0.12 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Overall 6.2e-05% 1/1,614,130 alleles · very rare exomes 1/1,461,878 · genomes 0/152,252 · joint denominator

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.Asp712Val
Coding: c.2135A>T
MANE Select: NM_004991
Type: single nucleotide variant
Location: chr3:169115737 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB

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.Asp712Ala Uncertain significance ★ ⚠ same residue
MECOM p.Asp712Glu Uncertain significance ★ ⚠ same residue
MECOM p.Asp712Tyr Uncertain significance ★ ⚠ same residue
MECOM p.Asp712= Likely benign ★ 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

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-asp712val (accessed [today's date]).

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