Is ALB p.Val442Met (c.1324G>A) pathogenic?

ALB p.Val442Met (c.1324G>A) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.2897); Very rare (popmax 0.00223%, eas).

How common is ALB p.Val442Met (c.1324G>A) in the general population?

ALB p.Val442Met (c.1324G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ALB p.Val442Met (c.1324G>A)?

AlphaMissense predicts likely benign (score 0.2897) — an in-silico prediction, not a clinical call.

ALB p.Val442Met

c.1324G>A · rs1257438609 · VCV2089553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2897 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2897	likely benign
REVEL	0.536	indeterminate
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.99, phastCons 0.97
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,850 alleles

Overall 0.000137% 2/1,461,796 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,850
South Asian	0.0011%	91,080

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.Val442Met
Coding: c.1324G>A
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs1257438609
Type: single nucleotide variant
Location: chr4:73417565 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 442: 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-val442met (accessed [today's date]).

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