Is MECOM p.Ser565fs (c.1692del) pathogenic?

MECOM p.Ser565fs (c.1692del) is classified Pathogenic in MECOM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-22). No gnomAD frequency available for this variant.

How common is MECOM p.Ser565fs (c.1692del) in the general population?

MECOM p.Ser565fs (c.1692del) is no gnomAD frequency available for this variant (gnomAD).

MECOM p.Ser565fs

c.1692del · rs2149078493 · VCV1454043

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MECOM
Protein: p.Ser565fs
Coding: c.1692del
MANE Select: NM_004991
dbSNP: rs2149078493
Type: Deletion
Location: chr3:169116180 (GRCh38)
Gene constraint: LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 51.04 · 1 PDB
Residue 565: the 'disordered' region

Full MECOM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MECOM c.3165-15del Benign/Likely benign ★★ same type
MECOM p.Asp864fs Pathogenic ★ same type
MECOM p.Gly799fs Likely pathogenic ★ same type
MECOM p.Gly802fs Likely pathogenic ★ same type
MECOM p.Lys835fs Pathogenic ★ same type
MECOM p.Phe958_Ser959delinsCys Uncertain significance ★ same type
MECOM c.2849+19del Likely benign ★ same type

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-ser565fs (accessed [today's date]).

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