Is MARVELD2 p.Arg10= (c.30G>A) pathogenic?

MARVELD2 p.Arg10= (c.30G>A) is classified Conflicting classifications of pathogenicity in MARVELD2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-07-13). Ultra-rare (popmax 0.0806%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 49.

What condition is associated with MARVELD2 p.Arg10= (c.30G>A)?

MARVELD2 p.Arg10= (c.30G>A) is associated with autosomal recessive nonsyndromic hearing loss 49 (ClinVar).

How common is MARVELD2 p.Arg10= (c.30G>A) in the general population?

MARVELD2 p.Arg10= (c.30G>A) is ultra-rare (popmax 0.0806%, nfe) (gnomAD).

MARVELD2 p.Arg10=

c.30G>A · rs143592561 · VCV195109

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0806%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 49

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.66, phastCons 0.99
Overall
CADD	8.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0806% European (non-Finnish) · 951/1,180,044 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0746%

Overall 0.0609% 983/1,613,992 alleles · ultra-rare exomes 947/1,461,890 · genomes 36/152,102 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0806%	1,241
Remaining individualsnot grpmax-eligible	0.0368%	2,717
African / African-American	0.00668%	14,974
Finnishnot grpmax-eligible	0.00469%	21,343
Admixed American	0.00167%	59,992

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: MARVELD2
Protein: p.Arg10=
Coding: c.30G>A
MANE Select: NM_001038603
dbSNP: rs143592561
Type: single nucleotide variant
Location: chr5:69419415 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.90 · 3 PDB
Residue 10: the 'disordered' region

Full MARVELD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 49 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MARVELD2 p.Arg10Trp Uncertain significance ★ ⚠ same residue
MARVELD2 c.1183-1G>A Pathogenic/Likely pathogenic ★★ same condition
MARVELD2 c.1331+1G>A Pathogenic ★★ same condition
MARVELD2 c.1331+2T>C Pathogenic/Likely pathogenic ★★ same condition
MARVELD2 p.Arg164Ter Likely pathogenic ★★ same condition
MARVELD2 p.Arg455Ter Likely pathogenic ★★ same condition
MARVELD2 p.Arg500Ter Pathogenic/Likely pathogenic ★★ same condition
MARVELD2 p.Ser63Ter Likely pathogenic ★★ same condition

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/marveld2-p-arg10 (accessed [today's date]).

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