Is ALB p.Ser226Arg (c.676A>C) pathogenic?

ALB p.Ser226Arg (c.676A>C) is classified Uncertain significance in ALB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-09). AlphaMissense: likely pathogenic (0.9539); Ultra-rare (popmax 0.0201%, eas); Associated with ALB-related disorder.

What condition is associated with ALB p.Ser226Arg (c.676A>C)?

ALB p.Ser226Arg (c.676A>C) is associated with ALB-related disorder (ClinVar).

How common is ALB p.Ser226Arg (c.676A>C) in the general population?

ALB p.Ser226Arg (c.676A>C) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about ALB p.Ser226Arg (c.676A>C)?

AlphaMissense predicts likely pathogenic (score 0.9539) — an in-silico prediction, not a clinical call.

ALB p.Ser226Arg

c.676A>C · VCV3348436

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9539 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALB-related disorder

Computational evidence

Protein change
AlphaMissense	0.9539	likely pathogenic · top 1% in ALB
REVEL	0.403	indeterminate
SaProt	LLR -3.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -1.4, phastCons 0.082
Overall
CADD	14.36	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 0.0201% East Asian · 9/44,878 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00062% 10/1,613,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
African / African-American	0.00133%	74,932

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.Ser226Arg
Coding: c.676A>C
MANE Select: NM_001319193 · reported on NM_000477
Type: single nucleotide variant
Location: chr4:73410372 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 226: the 'disordered' region

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

Disease context

ALB-related disorder

Similar variants

ALB p.Arg242His Conflicting classifications of pathogenicity ★ ⚠ same condition
ALB p.Glu594Lys Pathogenic ⚠ same condition
ALB p.Asn415Ile Uncertain significance ⚠ same condition
ALB p.Val78fs Pathogenic ★★ same condition
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

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-ser226arg (accessed [today's date]).

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