Is SAG p.Pro274Ser (c.820C>T) pathogenic?

SAG p.Pro274Ser (c.820C>T) is classified Uncertain significance in SAG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1219); Ultra-rare (popmax 0.066%, mid); Associated with Oguchi disease.

What condition is associated with SAG p.Pro274Ser (c.820C>T)?

SAG p.Pro274Ser (c.820C>T) is associated with Oguchi disease, retinitis pigmentosa (ClinVar).

How common is SAG p.Pro274Ser (c.820C>T) in the general population?

SAG p.Pro274Ser (c.820C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about SAG p.Pro274Ser (c.820C>T)?

AlphaMissense predicts likely benign (score 0.1219) — an in-silico prediction, not a clinical call.

SAG p.Pro274Ser

c.820C>T · rs369789189 · VCV335070

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1219 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Oguchi disease

Computational evidence

Protein change
AlphaMissense	0.1219	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00483% 78/1,613,964 alleles · ultra-rare exomes 71/1,461,634 · genomes 7/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
South Asian	0.011%	9,108
European (non-Finnish)	0.00534%	18,728
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Pro274Ser
Coding: c.820C>T
MANE Select: NM_000541
dbSNP: rs369789189
Type: single nucleotide variant
Location: chr2:233334975 (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-pro274ser (accessed [today's date]).

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