Is PDE6C p.Pro156Ser (c.466C>T) pathogenic?

PDE6C p.Pro156Ser (c.466C>T) is classified Conflicting classifications of pathogenicity in PDE6C (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-29). AlphaMissense: likely benign (0.1167); Rare (popmax 0.255%, afr); Associated with achromatopsia.

What condition is associated with PDE6C p.Pro156Ser (c.466C>T)?

PDE6C p.Pro156Ser (c.466C>T) is associated with achromatopsia, cone dystrophy 4 (ClinVar).

How common is PDE6C p.Pro156Ser (c.466C>T) in the general population?

PDE6C p.Pro156Ser (c.466C>T) is rare (popmax 0.255%, afr) (gnomAD).

How is Achromatopsia inherited?

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

What do computational predictors say about PDE6C p.Pro156Ser (c.466C>T)?

AlphaMissense predicts likely benign (score 0.1167) — an in-silico prediction, not a clinical call.

PDE6C p.Pro156Ser

c.466C>T · rs145591492 · VCV880177

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1167 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.255%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

achromatopsia

Computational evidence

Protein change
AlphaMissense	0.1167	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -8.01	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 2.2	GERP 2.2, phastCons 0.98
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.255% African / African-American · 191/74,986 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.214%

Overall 0.0139% 224/1,613,582 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.255%	393
Admixed American	0.0233%	4,287
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.000847%	118,000

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.Pro156Ser
Coding: c.466C>T
MANE Select: NM_006204
dbSNP: rs145591492
Type: single nucleotide variant
Location: chr10:93613191 (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 156: the gaf 1 domain; a β-strand

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

Disease context

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

Also linked: cone dystrophy 4

For Achromatopsia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PDE6C p.Pro156Arg Uncertain significance ★ ⚠ same residue
PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.1269+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.2283+1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg238Ter Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg259Ter Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg29Trp 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/pde6c-p-pro156ser (accessed [today's date]).

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