Is ASB18 p.Ser149Arg (c.445A>C) pathogenic?

ASB18 p.Ser149Arg (c.445A>C) is classified Uncertain significance in ASB18 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.4641); Ultra-rare (popmax 0.0984%, sas).

How common is ASB18 p.Ser149Arg (c.445A>C) in the general population?

ASB18 p.Ser149Arg (c.445A>C) is ultra-rare (popmax 0.0984%, sas) (gnomAD).

What do computational predictors say about ASB18 p.Ser149Arg (c.445A>C)?

AlphaMissense predicts ambiguous (score 0.4641) — an in-silico prediction, not a clinical call.

ASB18 p.Ser149Arg

c.445A>C · rs773417237 · VCV2247892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0984%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4641	ambiguous
REVEL	0.089	moderately benign-leaning
SaProt	LLR -3.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -3.6, phastCons 0.58
Regional constraint	o/e 1.06	unconstrained · MANE · 69 kb · p 0.13 · regional, not allelic
Overall
CADD	22.6	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 0.0984% South Asian · 61/62,002 alleles

Filtering AF 0.0786% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0715%

Overall 0.00474% 66/1,392,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0984%	1,016
Remaining individualsnot grpmax-eligible	0.00753%	13,272
European (non-Finnish)	9.22e-05%	1,084,786

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.Ser149Arg
Coding: c.445A>C
MANE Select: NM_212556
dbSNP: rs773417237
Type: single nucleotide variant
Location: chr2:236237840 (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-ser149arg (accessed [today's date]).

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