Is SBDS p.Pro6Ala (c.16C>G) pathogenic?

SBDS p.Pro6Ala (c.16C>G) is classified Uncertain significance in SBDS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-16). AlphaMissense: likely pathogenic (0.9837); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SBDS p.Pro6Ala (c.16C>G)?

SBDS p.Pro6Ala (c.16C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SBDS p.Pro6Ala (c.16C>G) in the general population?

SBDS p.Pro6Ala (c.16C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SBDS p.Pro6Ala (c.16C>G)?

AlphaMissense predicts likely pathogenic (score 0.9837) — an in-silico prediction, not a clinical call.

SBDS p.Pro6Ala

c.16C>G · VCV4864066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9837	likely pathogenic
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -12.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 7,043 bp · p 0.00045 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SBDS
Protein: p.Pro6Ala
Coding: c.16C>G
MANE Select: NM_016038
Type: single nucleotide variant
Location: chr7:66995402 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 6 PDB
Residue 6: a turn

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.Pro6= Likely benign ★ 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-pro6ala (accessed [today's date]).

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