Is DIP2B p.Ser229Thr (c.685T>A) pathogenic?

DIP2B p.Ser229Thr (c.685T>A) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-22). AlphaMissense: likely benign (0.0614); Very rare (popmax 0.000169%, nfe); Associated with intellectual disability, FRA12A type.

What condition is associated with DIP2B p.Ser229Thr (c.685T>A)?

DIP2B p.Ser229Thr (c.685T>A) is associated with intellectual disability, FRA12A type (ClinVar).

How common is DIP2B p.Ser229Thr (c.685T>A) in the general population?

DIP2B p.Ser229Thr (c.685T>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DIP2B p.Ser229Thr (c.685T>A)?

AlphaMissense predicts likely benign (score 0.0614) — an in-silico prediction, not a clinical call.

DIP2B p.Ser229Thr

c.685T>A · rs1938911020 · VCV930932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, FRA12A type

Computational evidence

Protein change
AlphaMissense	0.0614	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.63, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	17.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,876 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: DIP2B
Protein: p.Ser229Thr
Coding: c.685T>A
MANE Select: NM_173602
dbSNP: rs1938911020
Type: single nucleotide variant
Location: chr12:50674518 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83
Residue 229: the 'disordered' region

Full DIP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, FRA12A type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIP2B p.Asp501Val Uncertain significance ★★ ⚠ same condition
DIP2B p.Pro513Ser Uncertain significance ★★ ⚠ same condition
DIP2B p.Val584Ile Uncertain significance ★★ ⚠ same condition
DIP2B c.1814-15T>C Benign ★★ same condition
DIP2B c.4355-32A>G Benign ★★ same condition
DIP2B p.Asn982= Benign ★★ same condition
DIP2B p.Ile1477= Benign ★★ same condition
DIP2B p.Pro1384= Benign/Likely benign ★★ same condition

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/dip2b-p-ser229thr (accessed [today's date]).

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