Is ALB p.Ser478= (c.1434C>T) pathogenic?

ALB p.Ser478= (c.1434C>T) is classified Likely benign in ALB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-31). Ultra-rare (popmax 0.0381%, nfe); Associated with hyperthyroxinemia, familial dysalbuminemic.

What condition is associated with ALB p.Ser478= (c.1434C>T)?

ALB p.Ser478= (c.1434C>T) is associated with hyperthyroxinemia, familial dysalbuminemic (ClinVar).

How common is ALB p.Ser478= (c.1434C>T) in the general population?

ALB p.Ser478= (c.1434C>T) is ultra-rare (popmax 0.0381%, nfe) (gnomAD).

ALB p.Ser478=

c.1434C>T · rs139400924 · VCV349632

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0381%, nfe)

Conditions

hyperthyroxinemia, familial dysalbuminemic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -3.5
Overall
CADD	11.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0381% European (non-Finnish) · 450/1,179,852 alleles

Filtering AF 0.0352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.034%

Overall 0.0291% 470/1,613,688 alleles · ultra-rare exomes 434/1,461,636 · genomes 36/152,052 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0381%	2,622
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00935%	10,696
Finnishnot grpmax-eligible	0.00469%	21,334
East Asian	0.00223%	44,878
Admixed American	0.00167%	59,946

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.Ser478=
Coding: c.1434C>T
MANE Select: NM_000477
dbSNP: rs139400924
Type: single nucleotide variant
Location: chr4:73418093 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 478: 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.Ser478Cys Uncertain significance ★ ⚠ same residue
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

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-ser478 (accessed [today's date]).

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