Is MARCKS p.183EA[3] (c.546TGAGGC[3]) pathogenic?

MARCKS p.183EA[3] (c.546TGAGGC[3]) is classified Benign in MARCKS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-09). Rare (popmax 0.577%, nfe).

How common is MARCKS p.183EA[3] (c.546TGAGGC[3]) in the general population?

MARCKS p.183EA[3] (c.546TGAGGC[3]) is rare (popmax 0.577%, nfe) (gnomAD).

MARCKS p.183EA[3]

c.546TGAGGC[3] · rs747922228 · VCV774449

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.577%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -3.8, phastCons 0.95
Overall
CADD	7.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.577% European (non-Finnish) · 6,577/1,140,260 alleles

Filtering AF 0.565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.56%

Overall 0.499% 7,666/1,536,544 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.12%	89
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)grpmax	0.577%	173
Remaining individualsnot grpmax-eligible	0.347%	289
South Asian	0.109%	916
Admixed American	0.103%	975
African / African-American	0.0961%	1,041
Middle Eastern	0.0561%	1,784
East Asian	0.0132%	7,591
Ashkenazi Jewishnot grpmax-eligible	0.00371%	26,918

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MARCKS
Protein: p.183EA[3]
Coding: c.546TGAGGC[3]
MANE Select: NM_002356
dbSNP: rs747922228
Type: Microsatellite
Location: chr6:113860125 (GRCh38)
Gene constraint: LOEUF 1.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.42 · 1 PDB

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

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/marcks-p-183ea-3 (accessed [today's date]).

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