Is PDE6C p.Arg102Trp (c.304C>T) pathogenic?

PDE6C p.Arg102Trp (c.304C>T) is classified Conflicting classifications of pathogenicity in PDE6C (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-16). AlphaMissense: ambiguous (0.4979); Very rare (popmax 0.00223%, eas); Associated with inherited retinal dystrophy.

What condition is associated with PDE6C p.Arg102Trp (c.304C>T)?

PDE6C p.Arg102Trp (c.304C>T) is associated with inherited retinal dystrophy, cone dystrophy 4, achromatopsia (ClinVar).

How common is PDE6C p.Arg102Trp (c.304C>T) in the general population?

PDE6C p.Arg102Trp (c.304C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PDE6C p.Arg102Trp (c.304C>T)?

AlphaMissense predicts ambiguous (score 0.4979) — an in-silico prediction, not a clinical call.

PDE6C p.Arg102Trp

c.304C>T · rs375795507 · VCV487696

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.4979	ambiguous
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -12.34	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	25.6	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 0.00223% East Asian · 1/44,892 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000372% 6/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
Admixed American	0.00167%	60,008
Finnishnot grpmax-eligible	0.00156%	64,010
South Asian	0.0011%	91,076
European (non-Finnish)	0.000169%	590,019

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.Arg102Trp
Coding: c.304C>T
MANE Select: NM_006204
dbSNP: rs375795507
Type: single nucleotide variant
Location: chr10:93613029 (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 102: the gaf 1 domain; a β-strand

Full PDE6C 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

Also linked: cone dystrophy 4 achromatopsia

Similar variants

PDE6C p.Arg102= Conflicting classifications of pathogenicity ★ same residue
PDE6C p.Arg102Gln Pathogenic ★ ⚠ same residue
PDE6C p.Arg102Gly 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

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-arg102trp (accessed [today's date]).

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