Is ASIP p.Ser99Arg (c.297C>G) pathogenic?

ASIP p.Ser99Arg (c.297C>G) is classified Uncertain significance in ASIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely pathogenic (0.6916); Very rare (popmax 0.00461%, eas).

How common is ASIP p.Ser99Arg (c.297C>G) in the general population?

ASIP p.Ser99Arg (c.297C>G) is very rare (popmax 0.00461%, eas) (gnomAD).

What do computational predictors say about ASIP p.Ser99Arg (c.297C>G)?

AlphaMissense predicts likely pathogenic (score 0.6916) — an in-silico prediction, not a clinical call.

ASIP p.Ser99Arg

c.297C>G · rs759460072 · VCV3130390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00461%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6916	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.26	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 1.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 406 kb · p 0.14 · regional, not allelic
Overall
CADD	23.8	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 0.00461% East Asian · 2/43,352 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000286%

Overall 0.000139% 2/1,438,600 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: ASIP
Protein: p.Ser99Arg
Coding: c.297C>G
MANE Select: NM_000687 · reported on NM_001672
dbSNP: rs759460072
Type: single nucleotide variant
Location: chr20:34269065 (GRCh38)

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

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/asip-p-ser99arg (accessed [today's date]).

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