Is ASB18 p.Pro42Ser (c.124C>T) pathogenic?

ASB18 p.Pro42Ser (c.124C>T) is classified Uncertain significance in ASB18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-25). AlphaMissense: likely benign (0.0927); Ultra-rare (popmax 0.0165%, mid).

How common is ASB18 p.Pro42Ser (c.124C>T) in the general population?

ASB18 p.Pro42Ser (c.124C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ASB18 p.Pro42Ser (c.124C>T)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

ASB18 p.Pro42Ser

c.124C>T · VCV3434724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.06	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 7.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 69 kb · p 0.13 · regional, not allelic
Overall
CADD	14.66	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,613,934 alleles · ultra-rare exomes 1/1,461,694 · genomes 0/152,240 · joint denominator

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: ASB18
Protein: p.Pro42Ser
Coding: c.124C>T
MANE Select: NM_212556
Type: single nucleotide variant
Location: chr2:236264222 (GRCh38)
Gene constraint: LOEUF 1.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50

Full ASB18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB18 p.Ala127Thr Uncertain significance ★ ⚠ same type
ASB18 p.Ala134Thr Uncertain significance ★ ⚠ same type
ASB18 p.Ala166Pro Uncertain significance ★ ⚠ same type
ASB18 p.Ala187Glu Uncertain significance ★ same type
ASB18 p.Ala196Thr Uncertain significance ★ ⚠ same type
ASB18 p.Ala288Gly Uncertain significance ★ ⚠ same type
ASB18 p.Ala317Thr Uncertain significance ★ ⚠ same type
ASB18 p.Ala321Gly 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/asb18-p-pro42ser (accessed [today's date]).

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