Is SAG p.Cys67= (c.201C>T) pathogenic?

SAG p.Cys67= (c.201C>T) is classified Benign/Likely benign in SAG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.34%, nfe); Associated with Oguchi disease.

What condition is associated with SAG p.Cys67= (c.201C>T)?

SAG p.Cys67= (c.201C>T) is associated with Oguchi disease, retinitis pigmentosa (ClinVar).

How common is SAG p.Cys67= (c.201C>T) in the general population?

SAG p.Cys67= (c.201C>T) is low-frequency (popmax 3.34%, nfe) (gnomAD).

SAG p.Cys67=

c.201C>T · rs72976383 · VCV335066

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.34%, nfe)

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 -1.9	GERP -2
Overall
CADD	14.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.34% European (non-Finnish) · 39,167/1,173,694 alleles

Filtering AF 3.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.3%

Overall 2.86% 45,767/1,600,228 alleles · low-frequency exomes 42,426/1,447,922 · genomes 3,341/152,306 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	11.6%	9
European (non-Finnish)grpmax	3.34%	30
Remaining individualsnot grpmax-eligible	2.7%	37
Middle Eastern	2.68%	37
Ashkenazi Jewishnot grpmax-eligible	2.67%	37
Finnishnot grpmax-eligible	1.99%	50
Admixed American	1.65%	60
South Asian	1.41%	71
African / African-American	0.544%	184
East Asian	0.0226%	4,424

Amish 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.Cys67=
Coding: c.201C>T
MANE Select: NM_000541
dbSNP: rs72976383
Type: single nucleotide variant
Location: chr2:233320649 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB
Residue 67: an α-helix

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 p.Cys67Trp 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
SAG c.944+5G>A Uncertain significance ★★ same condition
SAG p.Ala100Thr 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-cys67 (accessed [today's date]).

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