Is ADCY10 p.Phe752Ser (c.2255T>C) pathogenic?

ADCY10 p.Phe752Ser (c.2255T>C) is classified Uncertain significance in ADCY10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.4976); Ultra-rare (popmax 0.0824%, eas).

How common is ADCY10 p.Phe752Ser (c.2255T>C) in the general population?

ADCY10 p.Phe752Ser (c.2255T>C) is ultra-rare (popmax 0.0824%, eas) (gnomAD).

What do computational predictors say about ADCY10 p.Phe752Ser (c.2255T>C)?

AlphaMissense predicts ambiguous (score 0.4976) — an in-silico prediction, not a clinical call.

ADCY10 p.Phe752Ser

c.2255T>C · rs202177911 · VCV2523737

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4976 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4976	ambiguous
REVEL	0.235	benign-leaning
SaProt	LLR -9.02	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 95 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0824% East Asian · 37/44,890 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00242% 39/1,614,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0824%	1,213
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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: ADCY10
Protein: p.Phe752Ser
Coding: c.2255T>C
MANE Select: NM_018417
dbSNP: rs202177911
Type: single nucleotide variant
Location: chr1:167854406 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17 · 37 PDB

Full ADCY10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADCY10 c.1139+6T>G Uncertain significance ★★ same type
ADCY10 c.253+4A>G Uncertain significance ★★ same type
ADCY10 p.Ala103Ser Uncertain significance ★★ ⚠ same type
ADCY10 p.Ala1278Asp Uncertain significance ★★ ⚠ same type
ADCY10 p.Ala862Gly Uncertain significance ★★ ⚠ same type
ADCY10 p.Ala991Ser Uncertain significance ★★ ⚠ same type
ADCY10 p.Arg1207Trp Uncertain significance ★★ ⚠ same type
ADCY10 p.Arg1217His Uncertain significance ★★ ⚠ 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/adcy10-p-phe752ser (accessed [today's date]).

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