Is ADIPOQ p.Thr83= (c.249C>T) pathogenic?

ADIPOQ p.Thr83= (c.249C>T) is classified Likely benign in ADIPOQ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-22). Ultra-rare (popmax 0.0376%, nfe).

How common is ADIPOQ p.Thr83= (c.249C>T) in the general population?

ADIPOQ p.Thr83= (c.249C>T) is ultra-rare (popmax 0.0376%, nfe) (gnomAD).

ADIPOQ p.Thr83=

c.249C>T · rs76533408 · VCV730481

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0376%, nfe)

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 -4.9	GERP -4
Overall
CADD	3.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0376% European (non-Finnish) · 443/1,179,540 alleles

Filtering AF 0.0346% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.0313% 505/1,613,376 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
European (non-Finnish)grpmax	0.0376%	2,663
Finnishnot grpmax-eligible	0.0344%	2,910
Remaining individualsnot grpmax-eligible	0.0256%	3,904
African / African-American	0.0107%	9,378
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,780
South Asian	0.0066%	15,162
Admixed American	0.00333%	29,987

Amish 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: ADIPOQ
Protein: p.Thr83=
Coding: c.249C>T
MANE Select: NM_004797
dbSNP: rs76533408
Type: single nucleotide variant
Location: chr3:186854218 (GRCh38)
Gene constraint: LOEUF 1.655 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 3 PDB
Residue 83: the collagen-like domain; the 'disordered' region

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

Similar variants

ADIPOQ p.Gly38Asp Benign/Likely benign ★★ ⚠ same type
ADIPOQ p.Arg55His Uncertain significance ★ same type
ADIPOQ p.Asn244Ile Uncertain significance ★ ⚠ same type
ADIPOQ p.Asp179Asn Uncertain significance ★ ⚠ same type
ADIPOQ p.Asp229Glu Uncertain significance ★ ⚠ same type
ADIPOQ p.Asp70Asn Uncertain significance ★ ⚠ same type
ADIPOQ p.Glu120Asp Uncertain significance ★ ⚠ same type
ADIPOQ p.Glu220Ter 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/adipoq-p-thr83 (accessed [today's date]).

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