Is ALB p.Pro176Leu (c.527C>T) pathogenic?

ALB p.Pro176Leu (c.527C>T) is classified Uncertain significance in ALB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely pathogenic (0.8649); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALB p.Pro176Leu (c.527C>T)?

ALB p.Pro176Leu (c.527C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALB p.Pro176Leu (c.527C>T) in the general population?

ALB p.Pro176Leu (c.527C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ALB p.Pro176Leu (c.527C>T)?

AlphaMissense predicts likely pathogenic (score 0.8649) — an in-silico prediction, not a clinical call.

ALB p.Pro176Leu

c.527C>T · VCV3851096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8649	likely pathogenic · top 2% in ALB
REVEL	0.744	pathogenic-leaning
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.1, phastCons 0.94
Overall
CADD	26.7	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

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000991% 16/1,613,804 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
Admixed American	0.00167%	59,988
South Asian	0.0011%	91,076
European (non-Finnish)	0.00102%	98,322

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.Pro176Leu
Coding: c.527C>T
MANE Select: NM_001319193 · reported on NM_000477
Type: single nucleotide variant
Location: chr4:73409399 (GRCh38)
Structure: AlphaFold pLDDT 64.11
Residue 176: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALB p.Pro176= Likely benign ★ same residue
ALB p.Ala324Pro Uncertain significance ★★ ⚠ same condition
ALB p.Ala387Ser Uncertain significance ★★ ⚠ same condition
ALB p.Asp197Tyr Uncertain significance ★★ ⚠ same condition
ALB p.His27Pro Uncertain significance ★★ ⚠ same condition
ALB p.Thr590Ile Uncertain significance ★★ ⚠ same condition
ALB p.Ala150Ser Uncertain significance ★ ⚠ same condition
ALB p.Ala195Thr Uncertain significance ★ ⚠ 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-pro176leu (accessed [today's date]).

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