Is PDE7A p.Arg435Ser (c.1305G>C) pathogenic?

PDE7A p.Arg435Ser (c.1305G>C) is classified Uncertain significance in PDE7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: likely benign (0.2648); Very rare (popmax 0.00466%, nfe).

How common is PDE7A p.Arg435Ser (c.1305G>C) in the general population?

PDE7A p.Arg435Ser (c.1305G>C) is very rare (popmax 0.00466%, nfe) (gnomAD).

What do computational predictors say about PDE7A p.Arg435Ser (c.1305G>C)?

AlphaMissense predicts likely benign (score 0.2648) — an in-silico prediction, not a clinical call.

PDE7A p.Arg435Ser

c.1305G>C · VCV3887280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00466%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2648	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -4.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.43	GERP -1.4, phastCons 0.052
Regional constraint	o/e 0.81	unconstrained · MANE · 122 kb · p 3e-06 · regional, not allelic
Overall
CADD	14.95	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

Grpmax group 0.00466% European (non-Finnish) · 55/1,179,950 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00353% 57/1,613,962 alleles · very rare exomes 50/1,461,804 · genomes 7/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00466%	21,454
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,920

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: PDE7A
Protein: p.Arg435Ser
Coding: c.1305G>C
MANE Select: NM_001242318
Type: single nucleotide variant
Location: chr8:65719434 (GRCh38)

Full PDE7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/pde7a-p-arg435ser (accessed [today's date]).

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