Is MARK1 p.Ser573Phe (c.1718C>T) pathogenic?

MARK1 p.Ser573Phe (c.1718C>T) is classified Uncertain significance in MARK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.1287); Very rare (popmax 0.000766%, nfe).

How common is MARK1 p.Ser573Phe (c.1718C>T) in the general population?

MARK1 p.Ser573Phe (c.1718C>T) is very rare (popmax 0.000766%, nfe) (gnomAD).

What do computational predictors say about MARK1 p.Ser573Phe (c.1718C>T)?

AlphaMissense predicts likely benign (score 0.1287) — an in-silico prediction, not a clinical call.

MARK1 p.Ser573Phe

c.1718C>T · rs367565722 · VCV2333178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000766%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1287	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 43 kb · p 0.00032 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000766% European (non-Finnish) · 9/1,175,324 alleles

Filtering AF 0.00036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.00056% 9/1,608,194 alleles · very rare exomes 7/1,456,086 · genomes 2/152,108 · joint denominator

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: MARK1
Protein: p.Ser573Phe
Coding: c.1718C>T
MANE Select: NM_018650
dbSNP: rs367565722
Type: single nucleotide variant
Location: chr1:220652132 (GRCh38)
Gene constraint: LOEUF 0.577 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB
Residue 573: the 'disordered' region

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

Similar variants

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
MARK1 p.Arg42Trp 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-ser573phe (accessed [today's date]).

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