Is ASB10 p.Ile380Phe (c.1138A>T) pathogenic?

ASB10 p.Ile380Phe (c.1138A>T) is classified Uncertain significance in ASB10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-30). AlphaMissense: likely pathogenic (0.6607); Very rare (popmax 0.00137%, afr).

How common is ASB10 p.Ile380Phe (c.1138A>T) in the general population?

ASB10 p.Ile380Phe (c.1138A>T) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about ASB10 p.Ile380Phe (c.1138A>T)?

AlphaMissense predicts likely pathogenic (score 0.6607) — an in-silico prediction, not a clinical call.

ASB10 p.Ile380Phe

c.1138A>T · rs973068070 · VCV2293021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6607	likely pathogenic
REVEL	0.713	pathogenic-leaning
SaProt	LLR -8.78	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 4.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.61 · regional, not allelic
Overall
CADD	24.1	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 0.00137% African / African-American · 1/73,024 alleles

Overall 0.000193% 3/1,551,320 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,024
South Asian	0.00119%	84,064
European (non-Finnish)	8.72e-05%	1,146,956

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: ASB10
Protein: p.Ile380Phe
Coding: c.1138A>T
MANE Select: NM_001142459
dbSNP: rs973068070
Type: single nucleotide variant
Location: chr7:151176643 (GRCh38)
Gene constraint: LOEUF 1.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.98

Full ASB10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB10 p.Ile380Met Uncertain significance ★ ⚠ same residue
ASB10 p.Arg138Trp Uncertain significance ★★ ⚠ same type
ASB10 p.Arg434Cys Uncertain significance ★★ ⚠ same type
ASB10 p.Leu455Ile Uncertain significance ★★ ⚠ same type
ASB10 p.Phe416Leu Uncertain significance ★★ ⚠ same type
ASB10 p.Pro31Thr Uncertain significance ★★ ⚠ same type
ASB10 p.Pro346Ser Uncertain significance ★★ ⚠ same type
ASB10 p.Pro422Arg 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/asb10-p-ile380phe (accessed [today's date]).

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