Is MARK3 p.Ile122Phe (c.364A>T) pathogenic?

MARK3 p.Ile122Phe (c.364A>T) is classified Uncertain significance in MARK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely pathogenic (0.8023); Absent from gnomAD v4.1.

How common is MARK3 p.Ile122Phe (c.364A>T) in the general population?

MARK3 p.Ile122Phe (c.364A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MARK3 p.Ile122Phe (c.364A>T)?

AlphaMissense predicts likely pathogenic (score 0.8023) — an in-silico prediction, not a clinical call.

MARK3 p.Ile122Phe

c.364A>T · VCV3870624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8023 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8023	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -15.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.89 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: MARK3
Protein: p.Ile122Phe
Coding: c.364A>T
MANE Select: NM_001128918
Type: single nucleotide variant
Location: chr14:103451935 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.25 · 14 PDB
Residue 122: the protein kinase domain; a β-strand

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

Similar variants

MARK3 c.413-4A>G Benign ★★ same type
MARK3 c.1917-11A>G Uncertain significance ★ same type
MARK3 p.Ala373Ser Uncertain significance ★ ⚠ same type
MARK3 p.Ala481Gly Uncertain significance ★ ⚠ same type
MARK3 p.Ala739Val Uncertain significance ★ ⚠ same type
MARK3 p.Ala748Asp Uncertain significance ★ ⚠ same type
MARK3 p.Arg262Lys Uncertain significance ★ ⚠ same type
MARK3 p.Arg305Lys 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/mark3-p-ile122phe (accessed [today's date]).

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