Is MARK4 p.Ile634= (c.1902C>T) pathogenic?

MARK4 p.Ile634= (c.1902C>T) is classified Likely benign in MARK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). Very rare (popmax 0.0067%, amr).

How common is MARK4 p.Ile634= (c.1902C>T) in the general population?

MARK4 p.Ile634= (c.1902C>T) is very rare (popmax 0.0067%, amr) (gnomAD).

MARK4 p.Ile634=

c.1902C>T · VCV3293342

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0067%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.462	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Overall
CADD	16.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% Admixed American · 4/59,694 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000374% 6/1,605,522 alleles · very rare exomes 6/1,453,212 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0067%	14,924
East Asian	0.00225%	44,376
European (non-Finnish)	8.52e-05%	1,174,346

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: MARK4
Protein: p.Ile634=
Coding: c.1902C>T
MANE Select: NM_001199867
Type: single nucleotide variant
Location: chr19:45299835 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.97 · 2 PDB

Full MARK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MARK4 p.Leu226= Benign ★★ same type
MARK4 p.Thr461= Benign ★★ same type
MARK4 p.Ala168Ser Uncertain significance ★ ⚠ same type
MARK4 p.Ala389Val Uncertain significance ★ ⚠ same type
MARK4 p.Ala457Val Uncertain significance ★ ⚠ same type
MARK4 p.Ala462Val Uncertain significance ★ ⚠ same type
MARK4 p.Ala479Thr Uncertain significance ★ ⚠ same type
MARK4 p.Ala47Thr 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/mark4-p-ile634 (accessed [today's date]).

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