Is ASB18 p.Ser413Phe (c.1238C>T) pathogenic?

ASB18 p.Ser413Phe (c.1238C>T) is classified Uncertain significance in ASB18 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-07). AlphaMissense: ambiguous (0.4254); Very rare (popmax 0.000254%, nfe).

How common is ASB18 p.Ser413Phe (c.1238C>T) in the general population?

ASB18 p.Ser413Phe (c.1238C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ASB18 p.Ser413Phe (c.1238C>T)?

AlphaMissense predicts ambiguous (score 0.4254) — an in-silico prediction, not a clinical call.

ASB18 p.Ser413Phe

c.1238C>T · rs773073926 · VCV2294238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4254	ambiguous
REVEL	0.228	benign-leaning
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 69 kb · p 0.13 · regional, not allelic
Overall
CADD	28.3	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 0.000254% European (non-Finnish) · 3/1,179,362 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,440 alleles · very rare

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.Ser413Phe
Coding: c.1238C>T
MANE Select: NM_212556
dbSNP: rs773073926
Type: single nucleotide variant
Location: chr2:236195035 (GRCh38)
Gene constraint: LOEUF 1.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50
Residue 413: the socs box domain

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-ser413phe (accessed [today's date]).

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