Is ALB p.Lys305Glu (c.913A>G) pathogenic?

ALB p.Lys305Glu (c.913A>G) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: ambiguous (0.5085); Absent from gnomAD v4.1; Associated with hyperthyroxinemia, familial dysalbuminemic.

What condition is associated with ALB p.Lys305Glu (c.913A>G)?

ALB p.Lys305Glu (c.913A>G) is associated with hyperthyroxinemia, familial dysalbuminemic (ClinVar).

How common is ALB p.Lys305Glu (c.913A>G) in the general population?

ALB p.Lys305Glu (c.913A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALB p.Lys305Glu (c.913A>G)?

AlphaMissense predicts ambiguous (score 0.5085) — an in-silico prediction, not a clinical call.

ALB p.Lys305Glu

c.913A>G · rs377046738 · VCV349624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5085 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hyperthyroxinemia, familial dysalbuminemic

Computational evidence

Protein change
AlphaMissense	0.5085	ambiguous · top 9% in ALB
REVEL	0.572	indeterminate
SaProt	LLR -12.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.48, phastCons 1
Overall
CADD	21.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALB
Protein: p.Lys305Glu
Coding: c.913A>G
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs377046738
Type: single nucleotide variant
Location: chr4:73413489 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 305: the 'disordered' region

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.Lys305Gln Uncertain significance ★ ⚠ same residue
ALB p.Ala83Gly Uncertain significance ★★ ⚠ same condition
ALB p.Arg105His Uncertain significance ★★ ⚠ same condition
ALB p.Arg23Cys 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

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-lys305glu (accessed [today's date]).

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