Is PDE6B p.Phe777= (c.2331C>T) pathogenic?

PDE6B p.Phe777= (c.2331C>T) is classified Benign/Likely benign in PDE6B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.31%, afr); Associated with congenital stationary night blindness autosomal dominant 2.

How common is PDE6B p.Phe777= (c.2331C>T) in the general population?

PDE6B p.Phe777= (c.2331C>T) is low-frequency (popmax 3.31%, afr) (gnomAD).

PDE6B p.Phe777=

Q: What condition is associated with PDE6B p.Phe777= (c.2331C>T)?

PDE6B p.Phe777= (c.2331C>T) is associated with congenital stationary night blindness autosomal dominant 2, retinitis pigmentosa 40, retinitis pigmentosa (ClinVar).

c.2331C>T · rs35792756 · VCV349393

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.31%, afr)

Conditions

congenital stationary night blindness autosomal dominant 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -4.5
Overall
CADD	7.838	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.31% African / African-American · 2,483/74,976 alleles

Filtering AF 3.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.16%

Overall 0.176% 2,833/1,611,688 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.31%	30
Remaining individualsnot grpmax-eligible	0.256%	390
Admixed American	0.222%	451
Middle Eastern	0.033%	3,027
South Asian	0.00439%	22,759
European (non-Finnish)	0.00424%	23,561
East Asian	0.00223%	44,866

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: PDE6B
Protein: p.Phe777=
Coding: c.2331C>T
MANE Select: NM_000283
dbSNP: rs35792756
Type: single nucleotide variant
Location: chr4:666593 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 777: the pdease domain

Full PDE6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital stationary night blindness autosomal dominant 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 40 retinitis pigmentosa

Similar variants

PDE6B p.Phe777Leu Uncertain significance ★ ⚠ same residue
PDE6B c.1059+2T>G Likely pathogenic ★★ same condition
PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.1107+1G>T Likely pathogenic ★★ same condition
PDE6B c.1107+3A>G Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.1832+1G>T Pathogenic ★★ same condition
PDE6B c.1921-9C>G Pathogenic ★★ same condition
PDE6B c.2021+2T>G Pathogenic/Likely pathogenic ★★ 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/pde6b-p-phe777 (accessed [today's date]).

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