Is PDE1C p.Ala69= (c.207C>T) pathogenic?

PDE1C p.Ala69= (c.207C>T) is classified Benign in PDE1C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-04). Common (popmax 17.1%, eas) — too common for a highly-penetrant pathogenic allele.

PDE1C p.Ala69=

Q: How common is PDE1C p.Ala69= (c.207C>T) in the general population?

PDE1C p.Ala69= (c.207C>T) is common (popmax 17.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207C>T · rs61729940 · VCV1273903

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 17.1%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -0.81, phastCons 0.79
Overall
CADD	7.962	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.1% East Asian · 7,662/44,726 alleles

Filtering AF 16.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.7%

Overall 10.6% 170,403/1,605,504 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	17.1%	6
South Asian	15.8%	6
Ashkenazi Jewishnot grpmax-eligible	12%	8
Middle Eastern	11.7%	9
European (non-Finnish)	10.8%	9
Remaining individualsnot grpmax-eligible	10.7%	9
Admixed American	7.06%	14
Finnishnot grpmax-eligible	6.41%	16
Amishnot grpmax-eligible	3.63%	28
African / African-American	3.21%	31

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: PDE1C
Protein: p.Ala69=
Coding: c.207C>T
MANE Select: NM_001191057
dbSNP: rs61729940
Type: single nucleotide variant
Location: chr7:31880782 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.53

Full PDE1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE1C p.His69Leu Uncertain significance ★ same residue
PDE1C p.His69= Benign ★ same residue
PDE1C p.Arg45Gln Uncertain significance ★★ ⚠ same type
PDE1C p.His619Tyr Uncertain significance ★★ ⚠ same type
PPP1R17 p.Asp21Glu Uncertain significance ★★ ⚠ same type
PPP1R17 p.Gln8Arg Uncertain significance ★★ ⚠ same type
PDE1C c.1203+28A>G Benign ★★ same type
PDE1C p.Ala594= Benign ★★ 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/pde1c-p-ala69 (accessed [today's date]).

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