Is SPARC p.Phe235= (c.705C>T) pathogenic?

SPARC p.Phe235= (c.705C>T) is classified Likely benign in SPARC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-31). Very rare (popmax 0.00801%, afr).

How common is SPARC p.Phe235= (c.705C>T) in the general population?

SPARC p.Phe235= (c.705C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

SPARC p.Phe235=

c.705C>T · rs755476160 · VCV1929170

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

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 -5.1	GERP -8
Overall
CADD	3.452	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,928 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00192% 31/1,613,948 alleles · very rare exomes 24/1,461,758 · genomes 7/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,488
South Asian	0.0022%	45,539
European (non-Finnish)	0.00195%	51,302

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.Phe235=
Coding: c.705C>T
MANE Select: NM_003118
dbSNP: rs755476160
Type: single nucleotide variant
Location: chr5:151666390 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.07 · 4 PDB
Residue 235: an α-helix

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-phe235 (accessed [today's date]).

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