Is MARK4 p.Gly585= (c.1755G>T) pathogenic?

MARK4 p.Gly585= (c.1755G>T) is classified Uncertain significance in MARK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-01). Ultra-rare (popmax 0.0352%, mid).

How common is MARK4 p.Gly585= (c.1755G>T) in the general population?

MARK4 p.Gly585= (c.1755G>T) is ultra-rare (popmax 0.0352%, mid) (gnomAD).

MARK4 p.Gly585=

c.1755G>T · rs750746729 · VCV808596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0352%, mid)

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 0.71	GERP 1.4, phastCons 1
Overall
CADD	9.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0352% Middle Eastern · 2/5,674 alleles

Filtering AF 0.00618% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00272%

Overall 0.00188% 29/1,545,610 alleles · ultra-rare exomes 28/1,393,540 · genomes 1/152,070 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0352%	2,837
South Asian	0.00835%	11,983
Remaining individualsnot grpmax-eligible	0.00167%	59,870
European (non-Finnish)	0.00166%	60,241

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: MARK4
Protein: p.Gly585=
Coding: c.1755G>T
MANE Select: NM_001199867
dbSNP: rs750746729
Type: single nucleotide variant
Location: chr19:45297832 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.97 · 2 PDB
Residue 585: the 'disordered' region

Full MARK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MARK4 p.Leu226= Benign ★★ same type
MARK4 p.Thr461= Benign ★★ same type
MARK4 p.Ala168Ser Uncertain significance ★ ⚠ same type
MARK4 p.Ala389Val Uncertain significance ★ ⚠ same type
MARK4 p.Ala457Val Uncertain significance ★ ⚠ same type
MARK4 p.Ala462Val Uncertain significance ★ ⚠ same type
MARK4 p.Ala479Thr Uncertain significance ★ ⚠ same type
MARK4 p.Ala47Thr Uncertain significance ★ ⚠ 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/mark4-p-gly585 (accessed [today's date]).

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