Is ALB p.Phe533Leu (c.1597T>C) pathogenic?

ALB p.Phe533Leu (c.1597T>C) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-21). AlphaMissense: likely pathogenic (0.9404); Ultra-rare (popmax 0.0922%, sas).

How common is ALB p.Phe533Leu (c.1597T>C) in the general population?

ALB p.Phe533Leu (c.1597T>C) is ultra-rare (popmax 0.0922%, sas) (gnomAD).

What do computational predictors say about ALB p.Phe533Leu (c.1597T>C)?

AlphaMissense predicts likely pathogenic (score 0.9404) — an in-silico prediction, not a clinical call.

ALB p.Phe533Leu

c.1597T>C · rs538903199 · VCV2188930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9404 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9404	likely pathogenic · top 1% in ALB
REVEL	0.662	pathogenic-leaning
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Overall
CADD	24.6	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 0.0922% South Asian · 84/91,084 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00558% 90/1,614,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0922%	1,084
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	8.47e-05%	1,180,008

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.Phe533Leu
Coding: c.1597T>C
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs538903199
Type: single nucleotide variant
Location: chr4:73418256 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 533: the 'disordered' region

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

Similar variants

ALB p.Arg138Ter Pathogenic ★★ same type
ALB p.Ala324Pro Uncertain significance ★★ ⚠ same type
ALB p.Ala387Ser Uncertain significance ★★ ⚠ same type
ALB p.Ala83Gly Uncertain significance ★★ ⚠ same type
ALB p.Arg105His Uncertain significance ★★ ⚠ same type
ALB p.Arg23Cys Uncertain significance ★★ ⚠ same type
ALB p.Asp197Tyr Uncertain significance ★★ ⚠ same type
ALB p.Asp37Asn 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/alb-p-phe533leu (accessed [today's date]).

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