Is SPARC p.Ala3= (c.9C>A) pathogenic?

SPARC p.Ala3= (c.9C>A) is classified Likely benign in SPARC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). Very rare (popmax 0.000124%).

How common is SPARC p.Ala3= (c.9C>A) in the general population?

SPARC p.Ala3= (c.9C>A) is very rare (popmax 0.000124%) (gnomAD).

SPARC p.Ala3=

c.9C>A · rs2480221517 · VCV2792197

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 3.8, phastCons 1
Overall
CADD	12.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000124%

Overall 0.000124% 2/1,611,542 alleles · very rare exomes 2/1,459,234 · genomes 0/152,308 · 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: SPARC
Protein: p.Ala3=
Coding: c.9C>A
MANE Select: NM_003118
dbSNP: rs2480221517
Type: single nucleotide variant
Location: chr5:151676180 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07 · 4 PDB

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

Similar variants

SPARC p.Arg195Trp Uncertain significance ★★ ⚠ same type
SPARC p.Arg205Leu Uncertain significance ★★ ⚠ same type
SPARC p.Arg218Trp Uncertain significance ★★ ⚠ same type
SPARC p.Asn202Tyr Uncertain significance ★★ ⚠ same type
SPARC p.Asp115Tyr Uncertain significance ★★ ⚠ same type
SPARC p.Asp120Asn Uncertain significance ★★ ⚠ same type
SPARC p.Asp219Glu Uncertain significance ★★ ⚠ same type
SPARC p.Gly13Arg 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/sparc-p-ala3 (accessed [today's date]).

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