Is ADIPOR2 p.Pro80Ser (c.238C>T) pathogenic?

ADIPOR2 p.Pro80Ser (c.238C>T) is classified Uncertain significance in ADIPOR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: ambiguous (0.3466); Very rare (popmax 0.00223%, eas).

How common is ADIPOR2 p.Pro80Ser (c.238C>T) in the general population?

ADIPOR2 p.Pro80Ser (c.238C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ADIPOR2 p.Pro80Ser (c.238C>T)?

AlphaMissense predicts ambiguous (score 0.3466) — an in-silico prediction, not a clinical call.

ADIPOR2 p.Pro80Ser

c.238C>T · VCV4244328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.3466	ambiguous
REVEL	0.411	indeterminate
SaProt	LLR -9.91	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 8,176 bp · p 3.1e-18 · regional, not allelic
Overall
CADD	22.4	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 0.00223% East Asian · 1/44,886 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000992% 16/1,613,588 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,234
East Asiangrpmax	0.00223%	44,886
South Asian	0.0022%	45,487
European (non-Finnish)	0.000932%	107,252

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ADIPOR2
Protein: p.Pro80Ser
Coding: c.238C>T
MANE Select: NM_024551
Type: single nucleotide variant
Location: chr12:1772908 (GRCh38)
Gene constraint: LOEUF 0.636 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 8 PDB
Residue 80: a UniProt-annotated variant site (found in a patient with autism spectrum disorder; uncertain significance)

Full ADIPOR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADIPOR2 p.Gly377= Benign/Likely benign ★★ same type
ADIPOR2 p.Ala259Val Uncertain significance ★ ⚠ same type
ADIPOR2 p.Ala325Thr Uncertain significance ★ ⚠ same type
ADIPOR2 p.Arg31Gln Uncertain significance ★ ⚠ same type
ADIPOR2 p.Arg373His Uncertain significance ★ ⚠ same type
ADIPOR2 p.Arg8Gln Uncertain significance ★ ⚠ same type
ADIPOR2 p.Gly286Arg Uncertain significance ★ ⚠ same type
ADIPOR2 p.His62Pro 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/adipor2-p-pro80ser (accessed [today's date]).

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