Is MECOM p.Phe860= (c.2580C>T) pathogenic?

MECOM p.Phe860= (c.2580C>T) is classified Likely benign in MECOM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Rare (popmax 0.109%, eas); Associated with Inborn genetic diseases.

What condition is associated with MECOM p.Phe860= (c.2580C>T)?

MECOM p.Phe860= (c.2580C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MECOM p.Phe860= (c.2580C>T) in the general population?

MECOM p.Phe860= (c.2580C>T) is rare (popmax 0.109%, eas) (gnomAD).

MECOM p.Phe860=

c.2580C>T · rs199555172 · VCV2059540

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	13.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% East Asian · 49/44,802 alleles

Filtering AF 0.0849% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.008% 129/1,612,602 alleles · rare exomes 119/1,460,336 · genomes 10/152,266 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.109%	914
Middle Eastern	0.0496%	2,016
Admixed American	0.015%	6,652
Remaining individualsnot grpmax-eligible	0.0112%	8,920
European (non-Finnish)	0.005%	19,986
African / African-American	0.00267%	37,499

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.Phe860=
Coding: c.2580C>T
MANE Select: NM_004991
dbSNP: rs199555172
Type: single nucleotide variant
Location: chr3:169107950 (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.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
MECOM p.Ala688Asp 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-phe860 (accessed [today's date]).

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