Is SDCBP p.Val73Ala (c.218T>C) pathogenic?

SDCBP p.Val73Ala (c.218T>C) is classified Uncertain significance in SDCBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.088); Very rare (popmax 8.49e-05%, nfe).

How common is SDCBP p.Val73Ala (c.218T>C) in the general population?

SDCBP p.Val73Ala (c.218T>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about SDCBP p.Val73Ala (c.218T>C)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

SDCBP p.Val73Ala

c.218T>C · VCV4581512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.68, phastCons 0.99
Regional constraint	o/e 0.82	unconstrained · MANE · 17 kb · p 0.00061 · regional, not allelic
Overall
CADD	15.76	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 8.49e-05% European (non-Finnish) · 1/1,177,864 alleles

Overall 6.21e-05% 1/1,610,820 alleles · very rare exomes 1/1,458,476 · genomes 0/152,344 · 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: SDCBP
Protein: p.Val73Ala
Coding: c.218T>C
MANE Select: NM_005625
Type: single nucleotide variant
Location: chr8:58572292 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 83.46 · 65 PDB

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

Similar variants

SDCBP p.Ala94Thr Uncertain significance ★ ⚠ same type
SDCBP p.Ala94Val Uncertain significance ★ ⚠ same type
SDCBP p.Arg113His Uncertain significance ★ ⚠ same type
SDCBP p.Arg197Gln Uncertain significance ★ ⚠ same type
SDCBP p.Arg197Trp Uncertain significance ★ ⚠ same type
SDCBP p.Arg281Trp Uncertain significance ★ ⚠ same type
SDCBP p.Asp120Glu Uncertain significance ★ ⚠ same type
SDCBP p.Asp156Asn Uncertain significance ★ ⚠ same type

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/sdcbp-p-val73ala (accessed [today's date]).

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