Is ALB p.Asn482= (c.1446C>T) pathogenic?

ALB p.Asn482= (c.1446C>T) is classified Benign/Likely benign in ALB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-20). Ultra-rare (popmax 0.0669%, nfe); Associated with hyperthyroxinemia, familial dysalbuminemic.

What condition is associated with ALB p.Asn482= (c.1446C>T)?

ALB p.Asn482= (c.1446C>T) is associated with hyperthyroxinemia, familial dysalbuminemic (ClinVar).

How common is ALB p.Asn482= (c.1446C>T) in the general population?

ALB p.Asn482= (c.1446C>T) is ultra-rare (popmax 0.0669%, nfe) (gnomAD).

ALB p.Asn482=

c.1446C>T · rs59597814 · VCV349633

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, nfe)

Conditions

hyperthyroxinemia, familial dysalbuminemic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.103	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.086	GERP 0.073, phastCons 0.002
Overall
CADD	3.414	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0669% European (non-Finnish) · 790/1,179,990 alleles

Filtering AF 0.063% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0615%

Overall 0.067% 1,081/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.73%	137
Remaining individualsnot grpmax-eligible	0.0736%	1,358
European (non-Finnish)grpmax	0.0669%	1,494
Admixed American	0.035%	2,856
African / African-American	0.0107%	9,363

Ashkenazi Jewish 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: ALB
Protein: p.Asn482=
Coding: c.1446C>T
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs59597814
Type: single nucleotide variant
Location: chr4:73418105 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 482: the 'disordered' region

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

Disease context

hyperthyroxinemia, familial dysalbuminemic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALB p.Ala83Gly Uncertain significance ★★ ⚠ same condition
ALB p.Arg105His Uncertain significance ★★ ⚠ same condition
ALB p.Arg23Cys Uncertain significance ★★ ⚠ same condition
ALB p.Asp37Asn Uncertain significance ★★ ⚠ same condition
ALB p.Cys384Arg Uncertain significance ★★ ⚠ same condition
ALB p.Thr491Met Uncertain significance ★★ ⚠ same condition
ALB c.1191+11T>A Benign ★★ same condition
ALB c.1290-6T>C Benign/Likely benign ★★ 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/alb-p-asn482 (accessed [today's date]).

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