Is SAG p.Phe156= (c.468C>T) pathogenic?

SAG p.Phe156= (c.468C>T) is classified Conflicting classifications of pathogenicity in SAG (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0239%, nfe); Associated with retinitis pigmentosa.

What condition is associated with SAG p.Phe156= (c.468C>T)?

SAG p.Phe156= (c.468C>T) is associated with retinitis pigmentosa, Oguchi disease (ClinVar).

How common is SAG p.Phe156= (c.468C>T) in the general population?

SAG p.Phe156= (c.468C>T) is ultra-rare (popmax 0.0239%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SAG p.Phe156=

c.468C>T · rs375593027 · VCV167636

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0239%, nfe)

Conditions

retinitis pigmentosa

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 -20	GERP -3.2
Overall
CADD	0.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0239% European (non-Finnish) · 282/1,179,782 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.0183% 295/1,613,696 alleles · ultra-rare exomes 279/1,461,554 · genomes 16/152,142 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0239%	4,184
Remaining individualsnot grpmax-eligible	0.00801%	12,490
African / African-American	0.00668%	14,979
Admixed American	0.00333%	29,999
South Asian	0.0011%	91,086

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.Phe156=
Coding: c.468C>T
MANE Select: NM_000541
dbSNP: rs375593027
Type: single nucleotide variant
Location: chr2:233327153 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB

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

Disease context

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

Also linked: Oguchi disease

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SAG p.Phe156Leu 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-phe156 (accessed [today's date]).

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