Is ASB16 p.Pro114Ser (c.340C>T) pathogenic?

ASB16 p.Pro114Ser (c.340C>T) is classified Uncertain significance in ASB16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: ambiguous (0.4761); Ultra-rare (popmax 0.0242%, sas).

How common is ASB16 p.Pro114Ser (c.340C>T) in the general population?

ASB16 p.Pro114Ser (c.340C>T) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about ASB16 p.Pro114Ser (c.340C>T)?

AlphaMissense predicts ambiguous (score 0.4761) — an in-silico prediction, not a clinical call.

ASB16 p.Pro114Ser

c.340C>T · VCV3951231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Computational evidence

Protein change
AlphaMissense	0.4761	ambiguous
REVEL	0.605	indeterminate
SaProt	LLR -10.04	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 7,597 bp · p 0.012 · regional, not allelic
Overall
CADD	23.4	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 0.0242% South Asian · 22/91,024 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00174% 28/1,611,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,137
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	8.48e-05%	1,179,922

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.Pro114Ser
Coding: c.340C>T
MANE Select: NM_080863
Type: single nucleotide variant
Location: chr17:44172084 (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-pro114ser (accessed [today's date]).

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