Is IGHMBP2 p.Arg595= (c.1783C>A) pathogenic?

IGHMBP2 p.Arg595= (c.1783C>A) is classified Likely benign in IGHMBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-08). Ultra-rare (popmax 0.0165%, mid); Associated with autosomal recessive distal spinal muscular atrophy 1.

How common is IGHMBP2 p.Arg595= (c.1783C>A) in the general population?

IGHMBP2 p.Arg595= (c.1783C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

IGHMBP2 p.Arg595=

Q: What condition is associated with IGHMBP2 p.Arg595= (c.1783C>A)?

IGHMBP2 p.Arg595= (c.1783C>A) is associated with autosomal recessive distal spinal muscular atrophy 1, Charcot-Marie-Tooth disease axonal type 2S (ClinVar).

Q: How is Spinal muscular atrophy with respiratory distress type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1783C>A · rs746014167 · VCV2928044

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

autosomal recessive distal spinal muscular atrophy 1

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 5	GERP 1.6, phastCons 1
Overall
CADD	13.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,614,140 alleles · ultra-rare exomes 1/1,461,846 · genomes 0/152,294 · 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: IGHMBP2
Protein: p.Arg595=
Coding: c.1783C>A
MANE Select: NM_002180
dbSNP: rs746014167
Type: single nucleotide variant
Location: chr11:68936263 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.87 · 4 PDB
Residue 595: an α-helix; the upf1-type sf1b helicase c-terminal domain

Full IGHMBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive distal spinal muscular atrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2S

For Spinal muscular atrophy with respiratory distress type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

IGHMBP2 p.Arg595Gln Uncertain significance ★★ ⚠ same residue
IGHMBP2 p.Arg595Trp Uncertain significance ★★ ⚠ same residue
IGHMBP2 c.1061-2A>G Pathogenic ★★ same condition
IGHMBP2 c.1235+894C>A Pathogenic/Likely pathogenic ★★ same condition
IGHMBP2 c.1632+1G>T Likely pathogenic ★★ same condition
IGHMBP2 c.1633-2A>G Likely pathogenic ★★ same condition
IGHMBP2 c.2611+1G>T Pathogenic/Likely pathogenic ★★ same condition
IGHMBP2 c.449+1G>A 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/ighmbp2-p-arg595 (accessed [today's date]).

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