Is MARK1 p.Val80Ala (c.239T>C) pathogenic?

MARK1 p.Val80Ala (c.239T>C) is classified Uncertain significance in MARK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: ambiguous (0.4891); Absent from gnomAD v4.1.

How common is MARK1 p.Val80Ala (c.239T>C) in the general population?

MARK1 p.Val80Ala (c.239T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MARK1 p.Val80Ala (c.239T>C)?

AlphaMissense predicts ambiguous (score 0.4891) — an in-silico prediction, not a clinical call.

MARK1 p.Val80Ala

c.239T>C · rs1664090855 · VCV2311907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4891	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -13.21	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 70 kb · p 0.014 · regional, not allelic
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MARK1
Protein: p.Val80Ala
Coding: c.239T>C
MANE Select: NM_018650
dbSNP: rs1664090855
Type: single nucleotide variant
Location: chr1:220579541 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB
Residue 80: the protein kinase domain; a turn

Full MARK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MARK1 p.Val80Ile Uncertain significance ★ ⚠ same residue
MARK1 p.Arg577Gln Uncertain significance ★★ ⚠ same type
MARK1 p.Ala541Pro Benign ★★ same type
MARK1 p.Ala352Thr Uncertain significance ★ ⚠ same type
MARK1 p.Ala442Asp Uncertain significance ★ ⚠ same type
MARK1 p.Arg268Gln Uncertain significance ★ ⚠ same type
MARK1 p.Arg391Gln Uncertain significance ★ ⚠ same type
MARK1 p.Arg421Cys 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/mark1-p-val80ala (accessed [today's date]).

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