Is ADCY6 p.Pro173= (c.519C>G) pathogenic?

ADCY6 p.Pro173= (c.519C>G) is classified Likely benign in ADCY6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.113%, amr).

How common is ADCY6 p.Pro173= (c.519C>G) in the general population?

ADCY6 p.Pro173= (c.519C>G) is rare (popmax 0.113%, amr) (gnomAD).

ADCY6 p.Pro173=

c.519C>G · rs561521194 · VCV734417

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.113%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -11	GERP -5
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% Admixed American · 68/59,988 alleles

Filtering AF 0.0917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0838%

Overall 0.00421% 68/1,613,382 alleles · rare exomes 66/1,461,130 · genomes 2/152,252 · joint denominator

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: ADCY6
Protein: p.Pro173=
Coding: c.519C>G
MANE Select: NM_015270
dbSNP: rs561521194
Type: single nucleotide variant
Location: chr12:48782916 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.33

Full ADCY6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCY6 p.Arg1065Trp Uncertain significance ★★ ⚠ same type
ADCY6 p.Arg538His Uncertain significance ★★ ⚠ same type
ADCY6 c.1376+168C>T Benign ★★ same type
ADCY6 c.1377-56G>A Benign ★★ same type
ADCY6 c.1833-29A>T Benign ★★ same type
ADCY6 c.1981-11C>G Benign ★★ same type
ADCY6 c.2283+57C>G Benign ★★ same type
ADCY6 c.2442+40G>T 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/adcy6-p-pro173 (accessed [today's date]).

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