Is MARK3 p.Arg38Gln (c.113G>A) pathogenic?

MARK3 p.Arg38Gln (c.113G>A) is classified Uncertain significance in MARK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely pathogenic (0.6878); Ultra-rare (popmax 0.0911%, sas).

How common is MARK3 p.Arg38Gln (c.113G>A) in the general population?

MARK3 p.Arg38Gln (c.113G>A) is ultra-rare (popmax 0.0911%, sas) (gnomAD).

What do computational predictors say about MARK3 p.Arg38Gln (c.113G>A)?

AlphaMissense predicts likely pathogenic (score 0.6878) — an in-silico prediction, not a clinical call.

MARK3 p.Arg38Gln

c.113G>A · rs569205142 · VCV2407783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0911%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6878	likely pathogenic
REVEL	0.355	indeterminate
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 66 kb · p 0.89 · regional, not allelic
Overall
CADD	26.5	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 0.0911% South Asian · 83/91,070 alleles

Filtering AF 0.0752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0694%

Overall 0.00694% 112/1,613,846 alleles · ultra-rare exomes 109/1,461,600 · genomes 3/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0911%	1,097
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00167%	59,934
European (non-Finnish)	0.00153%	65,551
African / African-American	0.00133%	74,992

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: MARK3
Protein: p.Arg38Gln
Coding: c.113G>A
MANE Select: NM_001128918
dbSNP: rs569205142
Type: single nucleotide variant
Location: chr14:103405137 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.25 · 14 PDB

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-arg38gln (accessed [today's date]).

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