Is SAG p.Ser4= (c.12C>T) pathogenic?

SAG p.Ser4= (c.12C>T) is classified Conflicting classifications of pathogenicity in SAG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-01). Very rare (popmax 0.00446%, eas); Associated with inherited retinal dystrophy.

What condition is associated with SAG p.Ser4= (c.12C>T)?

SAG p.Ser4= (c.12C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is SAG p.Ser4= (c.12C>T) in the general population?

SAG p.Ser4= (c.12C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

SAG p.Ser4=

c.12C>T · rs1700011294 · VCV1908380

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

inherited retinal dystrophy

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	10.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,860 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000682% 11/1,613,236 alleles · very rare exomes 9/1,461,136 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,430
African / African-American	0.00401%	24,955
South Asian	0.0011%	90,996
European (non-Finnish)	0.000424%	235,909

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.Ser4=
Coding: c.12C>T
MANE Select: NM_000541
dbSNP: rs1700011294
Type: single nucleotide variant
Location: chr2:233309201 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB
Residue 4: the 'disordered' region

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SAG p.Arg193Ter Pathogenic ★★ same condition
SAG p.Ala101Val Uncertain significance ★★ ⚠ same condition
SAG p.Arg322Gln Uncertain significance ★★ ⚠ same condition
SAG p.Arg358His Uncertain significance ★★ ⚠ same condition
SAG p.Phe379Ser Uncertain significance ★★ ⚠ same condition
SAG p.Ser146Tyr Uncertain significance ★★ ⚠ same condition
SAG p.Val228Met Uncertain significance ★★ ⚠ same condition
SAG p.Val378Ile 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-ser4 (accessed [today's date]).

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