Is ALB p.His91Arg (c.272A>G) pathogenic?

ALB p.His91Arg (c.272A>G) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: ambiguous (0.3449); Very rare (popmax 0.0011%, sas).

How common is ALB p.His91Arg (c.272A>G) in the general population?

ALB p.His91Arg (c.272A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ALB p.His91Arg (c.272A>G)?

AlphaMissense predicts ambiguous (score 0.3449) — an in-silico prediction, not a clinical call.

ALB p.His91Arg

c.272A>G · rs773096498 · VCV1416088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.3449	ambiguous
REVEL	0.343	indeterminate
SaProt	LLR -2.09	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -2.7, phastCons 1
Overall
CADD	13.43	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 0.0011% South Asian · 1/91,060 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,522 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,060
European (non-Finnish)	0.000509%	196,632

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.His91Arg
Coding: c.272A>G
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs773096498
Type: single nucleotide variant
Location: chr4:73408595 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 91: 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-his91arg (accessed [today's date]).

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