Is MECOM p.Arg969= (c.2907C>A) pathogenic?

MECOM p.Arg969= (c.2907C>A) is classified Likely benign in MECOM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-28). Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Arg969= (c.2907C>A)?

MECOM p.Arg969= (c.2907C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Arg969= (c.2907C>A) in the general population?

MECOM p.Arg969= (c.2907C>A) is very rare (popmax 0.00893%, eas) (gnomAD).

MECOM p.Arg969=

c.2907C>A · VCV4826705

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

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 0.25	GERP -4.6, phastCons 0.94
Overall
CADD	3.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,790 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,613,528 alleles · very rare exomes 4/1,461,240 · genomes 0/152,288 · 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.Arg969=
Coding: c.2907C>A
MANE Select: NM_004991
Type: single nucleotide variant
Location: chr3:169095188 (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.Arg969His Pathogenic ★ same residue
MECOM p.Arg969Leu Likely pathogenic ★ same residue
MECOM p.Arg969Cys Pathogenic 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-arg969 (accessed [today's date]).

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