Is PDE1C p.Glu157= (c.471G>A) pathogenic?

PDE1C p.Glu157= (c.471G>A) is classified Benign in PDE1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-05). Common (popmax 80.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hearing loss, autosomal dominant 74.

What condition is associated with PDE1C p.Glu157= (c.471G>A)?

PDE1C p.Glu157= (c.471G>A) is associated with hearing loss, autosomal dominant 74 (ClinVar).

PDE1C p.Glu157=

Q: How common is PDE1C p.Glu157= (c.471G>A) in the general population?

PDE1C p.Glu157= (c.471G>A) is common (popmax 80.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.471G>A · rs977626 · VCV1251668

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 80.8%, eas) — too common for a highly-penetrant pathogenic allele

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 0.83	GERP -3.4, phastCons 1
Overall
CADD	5.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 80.8% East Asian · 36,226/44,830 alleles

Filtering AF 80.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 79.8%

Overall 41.9% 674,669/1,611,204 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	80.8%	1
South Asian	64.8%	2
African / African-American	53.4%	2
Middle Eastern	48.6%	2
Finnishnot grpmax-eligible	45.6%	2
Remaining individualsnot grpmax-eligible	43.2%	2
Ashkenazi Jewishnot grpmax-eligible	39%	3
European (non-Finnish)	38%	3
Admixed American	35%	3
Amishnot grpmax-eligible	25.2%	4

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.Glu157=
Coding: c.471G>A
MANE Select: NM_001191057 · reported on NM_001322059
dbSNP: rs977626
Type: single nucleotide variant
Location: chr7:32169847 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.53
Residue 157: 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.Gly610= Benign ★★ same condition
PDE1C p.Ser175= Benign/Likely 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-glu157 (accessed [today's date]).

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