Is PDE6C p.Arg102Gln (c.305G>A) pathogenic?

PDE6C p.Arg102Gln (c.305G>A) is classified Pathogenic in PDE6C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). AlphaMissense: likely benign (0.3371); Very rare (popmax 0.00167%, amr).

How common is PDE6C p.Arg102Gln (c.305G>A) in the general population?

PDE6C p.Arg102Gln (c.305G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PDE6C p.Arg102Gln (c.305G>A)?

AlphaMissense predicts likely benign (score 0.3371) — an in-silico prediction, not a clinical call.

PDE6C p.Arg102Gln

c.305G>A · rs1441591017 · VCV1458687

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3371 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3371	likely benign ⚠ discordant with ClinVar
REVEL	0.511	indeterminate
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	29.9	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 0.00167% Admixed American · 1/60,022 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00109% 16/1,461,870 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
European (non-Finnish)	0.00127%	78,669

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.Arg102Gln
Coding: c.305G>A
MANE Select: NM_006204
dbSNP: rs1441591017
Type: single nucleotide variant
Location: chr10:93613030 (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

Similar variants

PDE6C p.Arg102= Conflicting classifications of pathogenicity ★ same residue
PDE6C p.Arg102Gly Uncertain significance ★ ⚠ same residue
PDE6C p.Arg102Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same type
PDE6C c.1269+1G>A Pathogenic/Likely pathogenic ★★ same type
PDE6C c.2283+1G>T Pathogenic/Likely pathogenic ★★ same type
PDE6C c.481-1G>A Likely pathogenic ★★ same type
PDE6C c.939+2T>G Pathogenic/Likely pathogenic ★★ same type

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-arg102gln (accessed [today's date]).

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