Is MECOM p.Ser252= (c.756C>T) pathogenic?

MECOM p.Ser252= (c.756C>T) is classified Benign/Likely benign in MECOM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Rare (popmax 0.411%, sas); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Ser252= (c.756C>T)?

MECOM p.Ser252= (c.756C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Ser252= (c.756C>T) in the general population?

MECOM p.Ser252= (c.756C>T) is rare (popmax 0.411%, sas) (gnomAD).

MECOM p.Ser252=

c.756C>T · rs539169252 · VCV722182

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.411%, 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 -0.29	GERP -4.9
Overall
CADD	3.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.411% South Asian · 374/91,068 alleles

Filtering AF 0.376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.363%

Overall 0.0297% 480/1,613,956 alleles · rare exomes 464/1,461,784 · genomes 16/152,172 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.411%	243
Middle Eastern	0.182%	551
Remaining individualsnot grpmax-eligible	0.0224%	4,464
European (non-Finnish)	0.00636%	15,732
Admixed American	0.005%	20,005
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
African / African-American	0.00267%	37,498

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.Ser252=
Coding: c.756C>T
MANE Select: NM_004991
dbSNP: rs539169252
Type: single nucleotide variant
Location: chr3:169127918 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 252: 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.Ser252Asn Uncertain significance ★★ ⚠ same residue
MECOM p.Ser252Arg 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
MECOM p.Ala537Thr 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-ser252 (accessed [today's date]).

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