Is SPARC p.Phe119= (c.357C>T) pathogenic?

SPARC p.Phe119= (c.357C>T) is classified Likely benign in SPARC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Rare (popmax 0.557%, eas).

How common is SPARC p.Phe119= (c.357C>T) in the general population?

SPARC p.Phe119= (c.357C>T) is rare (popmax 0.557%, eas) (gnomAD).

SPARC p.Phe119=

c.357C>T · rs779676614 · VCV744572

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.557%, eas)

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 -0.61	GERP -0.66
Overall
CADD	13.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.557% East Asian · 250/44,890 alleles

Filtering AF 0.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.478%

Overall 0.0162% 262/1,614,188 alleles · rare exomes 256/1,461,870 · genomes 6/152,318 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.557%	180
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,030
European (non-Finnish)	0.000763%	131,115

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.Phe119=
Coding: c.357C>T
MANE Select: NM_003118
dbSNP: rs779676614
Type: single nucleotide variant
Location: chr5:151669758 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07 · 4 PDB
Residue 119: the kazal-like domain; a β-strand

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-phe119 (accessed [today's date]).

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