Is SAG p.Arg175= (c.525A>G) pathogenic?

SAG p.Arg175= (c.525A>G) is classified Conflicting classifications of pathogenicity in SAG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.216%, nfe); Associated with retinitis pigmentosa.

What condition is associated with SAG p.Arg175= (c.525A>G)?

SAG p.Arg175= (c.525A>G) is associated with retinitis pigmentosa, Oguchi disease (ClinVar).

How common is SAG p.Arg175= (c.525A>G) in the general population?

SAG p.Arg175= (c.525A>G) is rare (popmax 0.216%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SAG p.Arg175=

c.525A>G · rs199839554 · VCV718731

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.216%, nfe)

Conditions

retinitis pigmentosa

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 -4.6	GERP -3.5
Overall
CADD	0.342	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.216% European (non-Finnish) · 2,546/1,179,606 alleles

Filtering AF 0.209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.206%

Overall 0.249% 4,022/1,613,588 alleles · rare exomes 3,609/1,461,306 · genomes 413/152,282 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.74%	58
Remaining individualsnot grpmax-eligible	0.293%	341
European (non-Finnish)grpmax	0.216%	463
South Asian	0.126%	792
Admixed American	0.0734%	1,363
African / African-American	0.028%	3,573
Middle Eastern	0.0165%	6,060

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SAG
Protein: p.Arg175=
Coding: c.525A>G
MANE Select: NM_000541
dbSNP: rs199839554
Type: single nucleotide variant
Location: chr2:233328490 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Oguchi disease

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SAG p.Arg175Ter Pathogenic ★ same residue
SAG p.Arg175Gln Uncertain significance ★ ⚠ same residue
SAG p.Arg175Leu Uncertain significance ★ ⚠ same residue
SAG c.1103-2A>C Pathogenic/Likely pathogenic ★★ same condition
SAG c.136+2T>G Pathogenic/Likely pathogenic ★★ same condition
SAG p.Arg193Ter Pathogenic ★★ same condition
SAG p.Arg292Ter Pathogenic ★★ same condition
SAG p.Gln191Ter Pathogenic/Likely pathogenic ★★ 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/sag-p-arg175 (accessed [today's date]).

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