Is ASB16 p.Pro320Ser (c.958C>T) pathogenic?

ASB16 p.Pro320Ser (c.958C>T) is classified Uncertain significance in ASB16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely pathogenic (0.5724); Very rare (popmax 0.00139%, afr).

How common is ASB16 p.Pro320Ser (c.958C>T) in the general population?

ASB16 p.Pro320Ser (c.958C>T) is very rare (popmax 0.00139%, afr) (gnomAD).

What do computational predictors say about ASB16 p.Pro320Ser (c.958C>T)?

AlphaMissense predicts likely pathogenic (score 0.5724) — an in-silico prediction, not a clinical call.

ASB16 p.Pro320Ser

c.958C>T · rs540563589 · VCV2492413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5724 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00139%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5724	likely pathogenic
REVEL	0.738	pathogenic-leaning
SaProt	LLR -11.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP -1.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 7,597 bp · p 0.012 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00139% African / African-American · 1/71,968 alleles

Overall 0.000132% 2/1,510,566 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00139%	71,968
South Asian	0.00125%	79,772

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: ASB16
Protein: p.Pro320Ser
Coding: c.958C>T
MANE Select: NM_080863
dbSNP: rs540563589
Type: single nucleotide variant
Location: chr17:44177126 (GRCh38)
Gene constraint: LOEUF 1.675 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.68

Full ASB16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB16 p.Ala200Pro Uncertain significance ★ ⚠ same type
ASB16 p.Ala200Thr Uncertain significance ★ ⚠ same type
ASB16 p.Ala219Val Uncertain significance ★ ⚠ same type
ASB16 p.Ala252Pro Uncertain significance ★ same type
ASB16 p.Ala254Thr Uncertain significance ★ ⚠ same type
ASB16 p.Ala273Gly Uncertain significance ★ ⚠ same type
ASB16 p.Ala291Thr Uncertain significance ★ ⚠ same type
ASB16 p.Ala310Thr 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/asb16-p-pro320ser (accessed [today's date]).

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