Is ASB10 p.Arg372Cys (c.1114C>T) pathogenic?

ASB10 p.Arg372Cys (c.1114C>T) is classified Benign in ASB10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.2547); Common (popmax 9.66%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ASB10 p.Arg372Cys (c.1114C>T)?

AlphaMissense predicts likely benign (score 0.2547) — an in-silico prediction, not a clinical call.

ASB10 p.Arg372Cys

Q: How common is ASB10 p.Arg372Cys (c.1114C>T) in the general population?

ASB10 p.Arg372Cys (c.1114C>T) is common (popmax 9.66%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1114C>T · rs62489646 · VCV677160

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2547 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.66%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2547	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -8.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.61 · regional, not allelic
Overall
CADD	27.7	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 9.66% African / African-American · 7,056/73,056 alleles

Filtering AF 9.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.39%

Overall 5.45% 84,463/1,550,106 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.66%	10
Finnishnot grpmax-eligible	7.79%	13
East Asian	7.57%	13
Ashkenazi Jewishnot grpmax-eligible	6.69%	15
Middle Eastern	6.53%	15
Remaining individualsnot grpmax-eligible	6.08%	16
European (non-Finnish)	5.13%	19
Admixed American	3.79%	26
South Asian	3.57%	28
Amishnot grpmax-eligible	1.1%	91

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.Arg372Cys
Coding: c.1114C>T
MANE Select: NM_001142459
dbSNP: rs62489646
Type: single nucleotide variant
Location: chr7:151176667 (GRCh38)
Gene constraint: LOEUF 1.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.98
Residue 372: a UniProt-annotated variant site (in)

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

Similar variants

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
ASB10 p.Pro451Leu 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-arg372cys (accessed [today's date]).

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