Is SAG p.Pro140= (c.420A>G) pathogenic?

SAG p.Pro140= (c.420A>G) is classified Conflicting classifications of pathogenicity in SAG (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-05). Rare (popmax 0.444%, afr); Associated with Oguchi disease.

What condition is associated with SAG p.Pro140= (c.420A>G)?

SAG p.Pro140= (c.420A>G) is associated with Oguchi disease, retinitis pigmentosa (ClinVar).

How common is SAG p.Pro140= (c.420A>G) in the general population?

SAG p.Pro140= (c.420A>G) is rare (popmax 0.444%, afr) (gnomAD).

SAG p.Pro140=

c.420A>G · rs150046934 · VCV769594

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.444%, afr)

Conditions

Oguchi disease

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 -8.2	GERP -3.8
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.444% African / African-American · 330/74,280 alleles

Filtering AF 0.405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.389%

Overall 0.0257% 405/1,575,132 alleles · rare exomes 203/1,422,830 · genomes 202/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.444%	225
Middle Eastern	0.083%	1,204
Admixed American	0.0556%	1,798
Remaining individualsnot grpmax-eligible	0.0376%	2,657
South Asian	0.00583%	17,159
European (non-Finnish)	0.000952%	105,093

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.Pro140=
Coding: c.420A>G
MANE Select: NM_000541
dbSNP: rs150046934
Type: single nucleotide variant
Location: chr2:233322990 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB

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

Disease context

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

Also linked: retinitis pigmentosa

Similar variants

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
SAG c.944+5G>A Uncertain significance ★★ same condition
SAG p.Ala100Thr Uncertain significance ★★ ⚠ same condition
SAG p.Ala289Val Uncertain significance ★★ ⚠ 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-pro140 (accessed [today's date]).

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