Is ASB1 p.Pro32Leu (c.95C>T) pathogenic?

ASB1 p.Pro32Leu (c.95C>T) is classified Uncertain significance in ASB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: ambiguous (0.416); Very rare (popmax 0.00329%, sas).

How common is ASB1 p.Pro32Leu (c.95C>T) in the general population?

ASB1 p.Pro32Leu (c.95C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ASB1 p.Pro32Leu (c.95C>T)?

AlphaMissense predicts ambiguous (score 0.416) — an in-silico prediction, not a clinical call.

ASB1 p.Pro32Leu

c.95C>T · rs780948993 · VCV2466620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.416 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
AlphaMissense	0.416	ambiguous
REVEL	0.303	indeterminate
SaProt	LLR -5.42	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.01 · regional, not allelic
Overall
CADD	26.6	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 0.00329% South Asian · 3/91,058 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000991% 16/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,353
European (non-Finnish)	0.0011%	90,770

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: ASB1
Protein: p.Pro32Leu
Coding: c.95C>T
MANE Select: NM_001040445
dbSNP: rs780948993
Type: single nucleotide variant
Location: chr2:238433599 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.61

Full ASB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB1 p.Ala11Gly Uncertain significance ★ ⚠ same type
ASB1 p.Ala216Val Uncertain significance ★ ⚠ same type
ASB1 p.Ala85Val Uncertain significance ★ ⚠ same type
ASB1 p.Arg141Trp Uncertain significance ★ ⚠ same type
ASB1 p.Arg144Cys Uncertain significance ★ ⚠ same type
ASB1 p.Arg144His Uncertain significance ★ ⚠ same type
ASB1 p.Arg156Gln Uncertain significance ★ ⚠ same type
ASB1 p.Arg165Ser 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/asb1-p-pro32leu (accessed [today's date]).

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