Is DIPK1B p.Ser96Pro (c.286T>C) pathogenic?

DIPK1B p.Ser96Pro (c.286T>C) is classified Uncertain significance in DIPK1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: ambiguous (0.5284); Very rare (popmax 0.00119%, nfe).

How common is DIPK1B p.Ser96Pro (c.286T>C) in the general population?

DIPK1B p.Ser96Pro (c.286T>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about DIPK1B p.Ser96Pro (c.286T>C)?

AlphaMissense predicts ambiguous (score 0.5284) — an in-silico prediction, not a clinical call.

DIPK1B p.Ser96Pro

c.286T>C · VCV3272120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5284	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -7.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.06 · regional, not allelic
Overall
CADD	22.4	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 0.00119% European (non-Finnish) · 14/1,179,910 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00093% 15/1,612,964 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00119%	84,279
South Asian	0.0011%	91,050

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: DIPK1B
Protein: p.Ser96Pro
Coding: c.286T>C
MANE Select: NM_152421
Type: single nucleotide variant
Location: chr9:136722008 (GRCh38)
Gene constraint: LOEUF 1.215 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.25
Residue 96: a disulfide bond

Full DIPK1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIPK1B p.Ala132Thr Uncertain significance ★ ⚠ same type
DIPK1B p.Ala172Val Uncertain significance ★ ⚠ same type
DIPK1B p.Ala218Thr Uncertain significance ★ ⚠ same type
DIPK1B p.Ala218Val Uncertain significance ★ ⚠ same type
DIPK1B p.Ala259Thr Uncertain significance ★ ⚠ same type
DIPK1B p.Ala272Thr Uncertain significance ★ ⚠ same type
DIPK1B p.Ala275Val Uncertain significance ★ ⚠ same type
DIPK1B p.Ala371Pro 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/dipk1b-p-ser96pro (accessed [today's date]).

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