Is SBDS p.Asp46= (c.138C>T) pathogenic?

SBDS p.Asp46= (c.138C>T) is classified Likely benign in SBDS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-14). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with SBDS p.Asp46= (c.138C>T)?

SBDS p.Asp46= (c.138C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SBDS p.Asp46= (c.138C>T) in the general population?

SBDS p.Asp46= (c.138C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

SBDS p.Asp46=

c.138C>T · VCV4864062

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 0.79, phastCons 1
Overall
CADD	13.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,066 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,613,852 alleles · very rare exomes 3/1,461,682 · genomes 0/152,170 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,533
European (non-Finnish)	8.48e-05%	1,179,880

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.Asp46=
Coding: c.138C>T
MANE Select: NM_016038
Type: single nucleotide variant
Location: chr7:66994332 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 6 PDB
Residue 46: 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.Asp46Asn 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-asp46 (accessed [today's date]).

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