Is SBDS p.Arg40= (c.118C>A) pathogenic?

SBDS p.Arg40= (c.118C>A) is classified Likely benign in SBDS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with SBDS p.Arg40= (c.118C>A)?

SBDS p.Arg40= (c.118C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SBDS p.Arg40= (c.118C>A) in the general population?

SBDS p.Arg40= (c.118C>A) is very rare (popmax 0.00891%, eas) (gnomAD).

SBDS p.Arg40=

c.118C>A · VCV3950307

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Overall
CADD	13.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,613,798 alleles · very rare exomes 5/1,461,434 · genomes 0/152,364 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
Admixed American	0.00167%	60,028

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: SBDS
Protein: p.Arg40=
Coding: c.118C>A
MANE Select: NM_016038
Type: single nucleotide variant
Location: chr7:66995300 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 6 PDB
Residue 40: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SBDS p.Arg40Gln Uncertain significance ★ ⚠ same residue
SBDS p.Lys33Thr Pathogenic/Likely pathogenic ★★ same condition
SBDS p.Arg22Cys Uncertain significance ★★ ⚠ same condition
SBDS p.Asp246Asn Uncertain significance ★★ ⚠ same condition
SBDS p.Cys216Tyr Uncertain significance ★★ ⚠ same condition
SBDS p.Ile111Val Uncertain significance ★★ ⚠ same condition
SBDS p.Ile224Thr Uncertain significance ★★ ⚠ same condition
SBDS p.Lys240Arg Uncertain significance ★★ ⚠ 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/sbds-p-arg40 (accessed [today's date]).

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