Is MARK3 p.Lys463= (c.1389G>A) pathogenic?

MARK3 p.Lys463= (c.1389G>A) is classified Benign in MARK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-25). Low-frequency (popmax 1.33%, nfe); Associated with MARK3-related disorder.

What condition is associated with MARK3 p.Lys463= (c.1389G>A)?

MARK3 p.Lys463= (c.1389G>A) is associated with MARK3-related disorder (ClinVar).

How common is MARK3 p.Lys463= (c.1389G>A) in the general population?

MARK3 p.Lys463= (c.1389G>A) is low-frequency (popmax 1.33%, nfe) (gnomAD).

MARK3 p.Lys463=

c.1389G>A · rs56126530 · VCV3044255

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.33%, nfe)

Conditions

MARK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.7, phastCons 1
Overall
CADD	8.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.33% European (non-Finnish) · 15,727/1,179,926 alleles

Filtering AF 1.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.31%

Overall 1.24% 20,092/1,614,090 alleles · low-frequency exomes 18,480/1,461,750 · genomes 1,612/152,340 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.83%	21
European (non-Finnish)grpmax	1.33%	75
Remaining individualsnot grpmax-eligible	1%	100
Middle Eastern	0.66%	151
Admixed American	0.275%	364
South Asian	0.272%	367
Ashkenazi Jewishnot grpmax-eligible	0.186%	538
African / African-American	0.181%	552
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00223%	44,886

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: MARK3
Protein: p.Lys463=
Coding: c.1389G>A
MANE Select: NM_001128918
dbSNP: rs56126530
Type: single nucleotide variant
Location: chr14:103475117 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.25 · 14 PDB
Residue 463: the 'disordered' region

Full MARK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MARK3-related disorder

Similar variants

MARK3 c.1586+4G>C Likely benign same condition
MARK3 c.412+4A>T Likely benign same condition
MARK3 p.Ala431= Benign same condition
MARK3 p.Asn632= Likely benign same condition
MARK3 p.Gln50= Likely benign same condition
MARK3 p.Gly296Arg Likely benign same condition
MARK3 p.Leu625= Likely benign same condition
MARK3 p.Ser443Gly Benign 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/mark3-p-lys463 (accessed [today's date]).

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