Is ALB p.Val557Met (c.1669G>A) pathogenic?

ALB p.Val557Met (c.1669G>A) is classified Uncertain significance in ALB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-04). AlphaMissense: ambiguous (0.3933); Ultra-rare (popmax 0.0828%, mid); Associated with Analbuminemia.

What condition is associated with ALB p.Val557Met (c.1669G>A)?

ALB p.Val557Met (c.1669G>A) is associated with Analbuminemia (ClinVar).

How common is ALB p.Val557Met (c.1669G>A) in the general population?

ALB p.Val557Met (c.1669G>A) is ultra-rare (popmax 0.0828%, mid) (gnomAD).

What do computational predictors say about ALB p.Val557Met (c.1669G>A)?

AlphaMissense predicts ambiguous (score 0.3933) — an in-silico prediction, not a clinical call.

ALB p.Val557Met

c.1669G>A · rs78284052 · VCV156313

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0828%, mid)

Conditions

Analbuminemia

Computational evidence

Protein change
AlphaMissense	0.3933	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -10.28	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -3, phastCons 0.96
Overall
CADD	21.4	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 0.0828% Middle Eastern · 5/6,042 alleles

Filtering AF 0.0458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0445%

Overall 0.0393% 633/1,610,426 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0828%	1,208
European (non-Finnish)	0.0491%	2,035
Remaining individualsnot grpmax-eligible	0.0465%	2,152
Admixed American	0.0201%	4,974
African / African-American	0.00404%	24,735
South Asian	0.0033%	30,314
East Asian	0.00223%	44,748
Finnishnot grpmax-eligible	0.00158%	63,470

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.Val557Met
Coding: c.1669G>A
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs78284052
Type: single nucleotide variant
Location: chr4:73419523 (GRCh38)
Structure: AlphaFold pLDDT 64.11

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

Disease context

Analbuminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALB p.Arg138Ter Pathogenic ★★ same condition
ALB c.1428+2T>C Likely pathogenic ★ same condition
ALB p.Arg24Gln Uncertain significance ★ ⚠ same condition
ALB p.Gln56Ter Pathogenic same condition
ALB p.Trp238Ter Pathogenic same condition
ALB p.Glu69Ter Likely pathogenic ★ same condition
ALB p.Lys219fs Likely pathogenic ★ same condition
ALB p.Val367fs Pathogenic 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-val557met (accessed [today's date]).

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