Is PDE6C p.Asp367Glu (c.1101T>G) pathogenic?

PDE6C p.Asp367Glu (c.1101T>G) is classified Uncertain significance in PDE6C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-03). AlphaMissense: ambiguous (0.4919); Very rare (popmax 0.00357%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PDE6C p.Asp367Glu (c.1101T>G)?

PDE6C p.Asp367Glu (c.1101T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PDE6C p.Asp367Glu (c.1101T>G) in the general population?

PDE6C p.Asp367Glu (c.1101T>G) is very rare (popmax 0.00357%, nfe) (gnomAD).

What do computational predictors say about PDE6C p.Asp367Glu (c.1101T>G)?

AlphaMissense predicts ambiguous (score 0.4919) — an in-silico prediction, not a clinical call.

PDE6C p.Asp367Glu

c.1101T>G · rs556892228 · VCV957466

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00357%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4919	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -8.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -4.1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	15.17	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 0.00357% European (non-Finnish) · 42/1,177,502 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.00261% 42/1,611,404 alleles · very rare

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.Asp367Glu
Coding: c.1101T>G
MANE Select: NM_006204
dbSNP: rs556892228
Type: single nucleotide variant
Location: chr10:93629287 (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 367: a UniProt-annotated variant site (in achm5); the gaf 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE6C p.Asp367= Likely benign ★ same residue
PDE6C p.Ala264Val Uncertain significance ★★ ⚠ same condition
PDE6C p.Ala462Val Uncertain significance ★★ ⚠ same condition
PDE6C p.Ala668Thr Uncertain significance ★★ ⚠ same condition
PDE6C p.Arg527Gln Uncertain significance ★★ ⚠ same condition
PDE6C p.Arg95Cys Uncertain significance ★★ ⚠ same condition
PDE6C p.Asn16Lys Uncertain significance ★★ ⚠ same condition
PDE6C p.Asn611Ser Uncertain significance ★★ ⚠ 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-asp367glu (accessed [today's date]).

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