Is MECOM p.Val343= (c.1029C>T) pathogenic?

MECOM p.Val343= (c.1029C>T) is classified Likely benign in MECOM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-23). Ultra-rare (popmax 0.0124%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Val343= (c.1029C>T)?

MECOM p.Val343= (c.1029C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Val343= (c.1029C>T) in the general population?

MECOM p.Val343= (c.1029C>T) is ultra-rare (popmax 0.0124%, nfe) (gnomAD).

MECOM p.Val343=

c.1029C>T · rs772780683 · VCV1338178

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, nfe)

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 -0.61	GERP -5
Overall
CADD	9.694	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0124% European (non-Finnish) · 146/1,179,722 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00998% 161/1,613,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0124%	8,080
Remaining individualsnot grpmax-eligible	0.00801%	12,490
Admixed American	0.00668%	14,978
African / African-American	0.00668%	14,981
East Asian	0.00223%	44,880

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.Val343=
Coding: c.1029C>T
MANE Select: NM_004991
dbSNP: rs772780683
Type: single nucleotide variant
Location: chr3:169121159 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 343: 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.Val343Ile 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
MECOM p.Ala653Val 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-val343 (accessed [today's date]).

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