Is PDE6C p.Ala700Thr (c.2098G>A) pathogenic?

PDE6C p.Ala700Thr (c.2098G>A) is classified Uncertain significance in PDE6C (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-30). AlphaMissense: likely benign (0.0761); Absent from gnomAD v4.1.

How common is PDE6C p.Ala700Thr (c.2098G>A) in the general population?

PDE6C p.Ala700Thr (c.2098G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE6C p.Ala700Thr (c.2098G>A)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

PDE6C p.Ala700Thr

c.2098G>A · rs2058653756 · VCV957175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.58	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 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	11.16	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDE6C
Protein: p.Ala700Thr
Coding: c.2098G>A
MANE Select: NM_006204
dbSNP: rs2058653756
Type: single nucleotide variant
Location: chr10:93658962 (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 700: a UniProt-annotated variant site (in achm5); the pdease domain; an α-helix

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

Similar variants

PDE6C p.Ala700Gly Uncertain significance ★ ⚠ 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
PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same type
PDE6C p.Arg104Trp 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-ala700thr (accessed [today's date]).

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