Is ALB p.Arg23Cys (c.67C>T) pathogenic?

ALB p.Arg23Cys (c.67C>T) is classified Uncertain significance in ALB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.6979); Ultra-rare (popmax 0.0149%, nfe); Associated with hyperthyroxinemia, familial dysalbuminemic.

What condition is associated with ALB p.Arg23Cys (c.67C>T)?

ALB p.Arg23Cys (c.67C>T) is associated with hyperthyroxinemia, familial dysalbuminemic (ClinVar).

How common is ALB p.Arg23Cys (c.67C>T) in the general population?

ALB p.Arg23Cys (c.67C>T) is ultra-rare (popmax 0.0149%, nfe) (gnomAD).

What do computational predictors say about ALB p.Arg23Cys (c.67C>T)?

AlphaMissense predicts likely pathogenic (score 0.6979) — an in-silico prediction, not a clinical call.

ALB p.Arg23Cys

c.67C>T · rs80008208 · VCV18213

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6979 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hyperthyroxinemia, familial dysalbuminemic

Computational evidence

Protein change
AlphaMissense	0.6979	likely pathogenic · top 5% in ALB
REVEL	0.504	indeterminate
SaProt	LLR -12.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0149% European (non-Finnish) · 176/1,178,626 alleles

Filtering AF 0.0131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0117% 189/1,612,254 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0149%	6,697
Remaining individualsnot grpmax-eligible	0.00961%	10,406
African / African-American	0.00535%	18,706
Finnishnot grpmax-eligible	0.00313%	31,979
Admixed American	0.00167%	59,966

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.Arg23Cys
Coding: c.67C>T
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs80008208
Type: single nucleotide variant
Location: chr4:73404394 (GRCh38)
Structure: AlphaFold pLDDT 64.11

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.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
ALB c.1785+7C>T 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-arg23cys (accessed [today's date]).

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