Is PDE1C p.Ser175= (c.525C>T) pathogenic?

PDE1C p.Ser175= (c.525C>T) is classified Benign/Likely benign in PDE1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-13). Low-frequency (popmax 2.78%, afr); Associated with hearing loss, autosomal dominant 74.

What condition is associated with PDE1C p.Ser175= (c.525C>T)?

PDE1C p.Ser175= (c.525C>T) is associated with hearing loss, autosomal dominant 74 (ClinVar).

How common is PDE1C p.Ser175= (c.525C>T) in the general population?

PDE1C p.Ser175= (c.525C>T) is low-frequency (popmax 2.78%, afr) (gnomAD).

PDE1C p.Ser175=

c.525C>T · rs76290787 · VCV708869

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.78%, afr)

Conditions

hearing loss, autosomal dominant 74

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 0.095	GERP -0.64, phastCons 0.75
Overall
CADD	7.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.78% African / African-American · 2,083/74,962 alleles

Filtering AF 2.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.163% 2,626/1,613,452 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.78%	36
Admixed American	0.357%	280
Remaining individualsnot grpmax-eligible	0.224%	446
Middle Eastern	0.149%	673
European (non-Finnish)	0.0148%	6,740
South Asian	0.00549%	18,209

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.Ser175=
Coding: c.525C>T
MANE Select: NM_001191057
dbSNP: rs76290787
Type: single nucleotide variant
Location: chr7:31873376 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.53
Residue 175: the pdease domain

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

Disease context

hearing loss, autosomal dominant 74 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE1C p.Arg45Gln Uncertain significance ★★ ⚠ same condition
PDE1C c.1203+28A>G Benign ★★ same condition
PDE1C p.Ala594= Benign ★★ same condition
PDE1C p.Asn591= Benign ★★ same condition
PDE1C p.Glu157= Benign ★★ same condition
PDE1C p.Gly610= Benign ★★ same condition
PDE1C c.86-1G>A Likely pathogenic ★ same condition
PDE1C p.Gln634Ter Likely pathogenic ★ 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/pde1c-p-ser175 (accessed [today's date]).

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