Is MARK2 p.Lys787Asn (c.2361G>T) pathogenic?

MARK2 p.Lys787Asn (c.2361G>T) is classified Uncertain significance in MARK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely pathogenic (0.8989); Ultra-rare (popmax 0.027%, amr).

How common is MARK2 p.Lys787Asn (c.2361G>T) in the general population?

MARK2 p.Lys787Asn (c.2361G>T) is ultra-rare (popmax 0.027%, amr) (gnomAD).

What do computational predictors say about MARK2 p.Lys787Asn (c.2361G>T)?

AlphaMissense predicts likely pathogenic (score 0.8989) — an in-silico prediction, not a clinical call.

MARK2 p.Lys787Asn

c.2361G>T · rs764981503 · VCV2372628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8989 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8989	likely pathogenic
REVEL	0.194	benign-leaning
SaProt	LLR -10.74	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP -0.58, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 157 bp · p 1.5e-06 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.027% Admixed American · 16/59,268 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00107% 17/1,585,070 alleles · ultra-rare exomes 14/1,432,860 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.027%	3,704
European (non-Finnish)	8.64e-05%	1,157,257

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: MARK2
Protein: p.Lys787Asn
Coding: c.2361G>T
MANE Select: NM_001039469
dbSNP: rs764981503
Type: single nucleotide variant
Location: chr11:63909231 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.21 · 5 PDB
Residue 787: the ka1 domain; a UniProt-annotated variant site (in mrd76; likely pathogenic); a UniProt-annotated variant site (in mrd76; pathogenic)

Full MARK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MARK2 p.Ala432Thr Uncertain significance ★★ ⚠ same type
MARK2 p.Arg264Ser Uncertain significance ★★ ⚠ same type
MARK2 p.Arg482Ter Uncertain significance ★★ same type
MARK2 c.337+8C>G Likely benign ★★ same type
MARK2 p.Pro459= Benign ★★ same type
MARK2 p.Pro740= Benign ★★ same type
MARK2 p.Ser725= Benign ★★ same type
MARK2 c.1102-1G>C Likely pathogenic ★ 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/mark2-p-lys787asn (accessed [today's date]).

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