Is ALB p.Phe398Ser (c.1193T>C) pathogenic?

ALB p.Phe398Ser (c.1193T>C) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.3212); Absent from gnomAD v4.1; Associated with hyperthyroxinemia, familial dysalbuminemic.

What condition is associated with ALB p.Phe398Ser (c.1193T>C)?

ALB p.Phe398Ser (c.1193T>C) is associated with hyperthyroxinemia, familial dysalbuminemic (ClinVar).

How common is ALB p.Phe398Ser (c.1193T>C) in the general population?

ALB p.Phe398Ser (c.1193T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALB p.Phe398Ser (c.1193T>C)?

AlphaMissense predicts likely benign (score 0.3212) — an in-silico prediction, not a clinical call.

ALB p.Phe398Ser

c.1193T>C · rs1719009522 · VCV906989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3212 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hyperthyroxinemia, familial dysalbuminemic

Computational evidence

Protein change
AlphaMissense	0.3212	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -6.33	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 5	GERP 1.9, phastCons 0.91
Overall
CADD	16.97	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

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.Phe398Ser
Coding: c.1193T>C
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs1719009522
Type: single nucleotide variant
Location: chr4:73416257 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 398: 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.Phe398= 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-phe398ser (accessed [today's date]).

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