Is SBDS p.Ser73Arg (c.217A>C) pathogenic?

SBDS p.Ser73Arg (c.217A>C) is classified Uncertain significance in SBDS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). AlphaMissense: likely benign (0.2259); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SBDS p.Ser73Arg (c.217A>C)?

SBDS p.Ser73Arg (c.217A>C) is associated with Inborn genetic diseases (ClinVar).

How common is SBDS p.Ser73Arg (c.217A>C) in the general population?

SBDS p.Ser73Arg (c.217A>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about SBDS p.Ser73Arg (c.217A>C)?

AlphaMissense predicts likely benign (score 0.2259) — an in-silico prediction, not a clinical call.

SBDS p.Ser73Arg

c.217A>C · rs1458246433 · VCV1787231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2259	likely benign
REVEL	0.394	indeterminate
SaProt	LLR -6.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 7,043 bp · p 0.00045 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,976 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,030 alleles · very rare exomes 2/1,461,808 · genomes 2/152,222 · 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: SBDS
Protein: p.Ser73Arg
Coding: c.217A>C
MANE Select: NM_016038
dbSNP: rs1458246433
Type: single nucleotide variant
Location: chr7:66994253 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 6 PDB
Residue 73: 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.Ser73Asn Uncertain significance ★ ⚠ same residue
SBDS p.Ser73Gly 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

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-ser73arg (accessed [today's date]).

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