Is PDE6B p.Gln237Arg (c.710A>G) pathogenic?

PDE6B p.Gln237Arg (c.710A>G) is classified Uncertain significance in PDE6B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-09). AlphaMissense: ambiguous (0.3863); Absent from gnomAD v4.1.

How common is PDE6B p.Gln237Arg (c.710A>G) in the general population?

PDE6B p.Gln237Arg (c.710A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDE6B p.Gln237Arg (c.710A>G)?

AlphaMissense predicts ambiguous (score 0.3863) — an in-silico prediction, not a clinical call.

PDE6B p.Gln237Arg

c.710A>G · rs2474110534 · VCV2751023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3863 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,583,118)

Computational evidence

Protein change
AlphaMissense	0.3863	ambiguous
REVEL	0.543	indeterminate
SaProt	LLR -5.43	tolerated
Splicing
SpliceAI	Δ0.70	donor loss · deltas
Pangolin	Δ0.62	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	27.7	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

No allele count reported in gnomAD v4.1 (AN 1,583,118). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDE6B
Protein: p.Gln237Arg
Coding: c.710A>G
MANE Select: NM_000283
dbSNP: rs2474110534
Type: single nucleotide variant
Location: chr4:635968 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 237: the gaf 2 domain

Full PDE6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE6B c.1059+2T>G Likely pathogenic ★★ same type
PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same type
PDE6B c.1107+1G>T Likely pathogenic ★★ same type
PDE6B c.1107+3A>G Pathogenic/Likely pathogenic ★★ same type
PDE6B c.1468-2A>G Pathogenic/Likely pathogenic ★★ same type
PDE6B c.1832+1G>T Pathogenic ★★ same type
PDE6B c.1921-1G>A Pathogenic ★★ same type
PDE6B c.1921-2A>G 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/pde6b-p-gln237arg (accessed [today's date]).

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