Is PDE6C p.Arg276Ter (c.826C>T) pathogenic?

PDE6C p.Arg276Ter (c.826C>T) is classified Pathogenic in PDE6C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2009-11-17). Very rare (popmax 0.004%, afr); Associated with achromatopsia 5.

What condition is associated with PDE6C p.Arg276Ter (c.826C>T)?

PDE6C p.Arg276Ter (c.826C>T) is associated with achromatopsia 5 (ClinVar).

How common is PDE6C p.Arg276Ter (c.826C>T) in the general population?

PDE6C p.Arg276Ter (c.826C>T) is very rare (popmax 0.004%, afr) (gnomAD).

PDE6C p.Arg276Ter

c.826C>T · rs267606937 · VCV8773

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

achromatopsia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -1, phastCons 0.24
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,916 alleles

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

Overall 0.000682% 11/1,613,796 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,972
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	59,992
European (non-Finnish)	0.000424%	235,975

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: PDE6C
Protein: p.Arg276Ter
Coding: c.826C>T
MANE Select: NM_006204
dbSNP: rs267606937
Type: single nucleotide variant
Location: chr10:93622034 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.53 · 7 PDB
Residue 276: a UniProt-annotated variant site (in achm5); the gaf 2 domain; a β-strand

Full PDE6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

achromatopsia 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE6C p.Arg276Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PDE6C p.Arg276= Likely benign ★ same residue
PDE6C p.Arg29Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
PDE6C p.Ile279Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
PDE6C c.1483-2A>G Pathogenic same condition
PDE6C c.481-12T>A Pathogenic same condition
PDE6C p.Glu211Asp Pathogenic ⚠ same condition
PDE6C p.Glu790Lys 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/pde6c-p-arg276ter (accessed [today's date]).

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