Is SAG p.Asp77= (c.231C>T) pathogenic?

SAG p.Asp77= (c.231C>T) is classified Conflicting classifications of pathogenicity in SAG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.67%, afr); Associated with Oguchi disease.

What condition is associated with SAG p.Asp77= (c.231C>T)?

SAG p.Asp77= (c.231C>T) is associated with Oguchi disease, retinitis pigmentosa (ClinVar).

How common is SAG p.Asp77= (c.231C>T) in the general population?

SAG p.Asp77= (c.231C>T) is low-frequency (popmax 1.67%, afr) (gnomAD).

SAG p.Asp77=

c.231C>T · rs79922016 · VCV719407

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.67%, afr)

Conditions

Oguchi disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -15	GERP -3.8
Overall
CADD	4.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.67% African / African-American · 1,249/74,916 alleles

Filtering AF 1.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.56%

Overall 0.1% 1,613/1,607,144 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.67%	60
Middle Eastern	0.297%	336
Admixed American	0.176%	567
Remaining individualsnot grpmax-eligible	0.125%	798
European (non-Finnish)	0.0133%	7,544
East Asian	0.00673%	14,865
South Asian	0.00447%	22,389
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,448

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.Asp77=
Coding: c.231C>T
MANE Select: NM_000541
dbSNP: rs79922016
Type: single nucleotide variant
Location: chr2:233320679 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB
Residue 77: a β-strand

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-asp77 (accessed [today's date]).

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