Is MECOM p.Ser784= (c.2352T>C) pathogenic?

MECOM p.Ser784= (c.2352T>C) is classified Benign/Likely benign in MECOM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-31). Low-frequency (popmax 1.53%, sas); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Ser784= (c.2352T>C)?

MECOM p.Ser784= (c.2352T>C) is associated with Inborn genetic diseases, radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (ClinVar).

How common is MECOM p.Ser784= (c.2352T>C) in the general population?

MECOM p.Ser784= (c.2352T>C) is low-frequency (popmax 1.53%, sas) (gnomAD).

MECOM p.Ser784=

c.2352T>C · rs370860789 · VCV1337894

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.53%, sas)

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 3.1	GERP -0.048, phastCons 1
Overall
CADD	7.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.53% South Asian · 1,396/91,064 alleles

Filtering AF 1.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.0901% 1,454/1,613,902 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.53%	65
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.00167%	59,982
European (non-Finnish)	0.000508%	196,667

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.Ser784=
Coding: c.2352T>C
MANE Select: NM_004991
dbSNP: rs370860789
Type: single nucleotide variant
Location: chr3:169115520 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 784: the 'disordered' 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

Also linked: radioulnar synostosis with amegakaryocytic thrombocytopenia 2

Similar variants

MECOM p.Ser784Gly Uncertain significance ★ ⚠ same residue
MECOM p.Arg938Trp Pathogenic/Likely pathogenic ★★ same condition
MECOM c.2577+4A>T Uncertain significance ★★ same condition
MECOM p.Ala1022Gly Uncertain significance ★★ ⚠ same condition
MECOM p.Ala1146Ser 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-ser784 (accessed [today's date]).

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