Is ALB p.Phe398= (c.1194C>T) pathogenic?

ALB p.Phe398= (c.1194C>T) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0134%, eas); Associated with hyperthyroxinemia, familial dysalbuminemic.

What condition is associated with ALB p.Phe398= (c.1194C>T)?

ALB p.Phe398= (c.1194C>T) is associated with hyperthyroxinemia, familial dysalbuminemic (ClinVar).

How common is ALB p.Phe398= (c.1194C>T) in the general population?

ALB p.Phe398= (c.1194C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ALB p.Phe398=

c.1194C>T · rs770952660 · VCV906990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

hyperthyroxinemia, familial dysalbuminemic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.61 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.9	GERP -3.7
Overall
CADD	0.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,790 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.00254% 41/1,611,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,465
African / African-American	0.00668%	14,965
Remaining individualsnot grpmax-eligible	0.00321%	31,201
European (non-Finnish)	0.00221%	45,329
Admixed American	0.00167%	59,930
Finnishnot grpmax-eligible	0.00156%	63,946

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.Phe398=
Coding: c.1194C>T
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs770952660
Type: single nucleotide variant
Location: chr4:73416258 (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.Phe398Ser 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-phe398 (accessed [today's date]).

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