Is ALB p.Val78fs (c.228_229del) pathogenic?

ALB p.Val78fs (c.228229del) is classified Pathogenic in ALB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-09-01). Very rare (popmax 0.00769%, sas); Associated with ALB-related disorder.

What condition is associated with ALB p.Val78fs (c.228_229del)?

ALB p.Val78fs (c.228_229del) is associated with ALB-related disorder (ClinVar).

How common is ALB p.Val78fs (c.228_229del) in the general population?

ALB p.Val78fs (c.228_229del) is very rare (popmax 0.00769%, sas) (gnomAD).

ALB p.Val78fs

c.228_229del · rs75152012 · VCV156319

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

ALB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.23	GERP 0.86
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,082 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00421% 68/1,613,748 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
European (non-Finnish)	0.00466%	21,454
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,458
East Asian	0.00223%	44,826

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.Val78fs
Coding: c.228_229del
MANE Select: NM_001319193 · reported on NM_000477
dbSNP: rs75152012
Type: Deletion
Location: chr4:73406719 (GRCh38)
Structure: AlphaFold pLDDT 64.11

Full ALB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALB-related disorder

Similar variants

ALB p.Arg242His Conflicting classifications of pathogenicity ★ ⚠ same condition
ALB p.Glu594Lys Pathogenic ⚠ same condition
ALB p.Asn415Ile Uncertain significance ⚠ same condition
ALB p.Ser226Arg Uncertain significance ⚠ same condition
ALB p.Lys219fs Likely pathogenic ★ same type
ALB c.*102_*108del Uncertain significance ★ same type
ALB c.615+26del Benign ★ same type
ALB c.843+25del Likely benign ★ 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-val78fs (accessed [today's date]).

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