Is DIP2B p.Ser354Pro (c.1060T>C) pathogenic?

DIP2B p.Ser354Pro (c.1060T>C) is classified Likely benign in DIP2B (ClinVar, Single submitter, 2 submitters; last evaluated 2017-07-21). AlphaMissense: likely benign (0.0375); Rare (popmax 0.214%, nfe).

How common is DIP2B p.Ser354Pro (c.1060T>C) in the general population?

DIP2B p.Ser354Pro (c.1060T>C) is rare (popmax 0.214%, nfe) (gnomAD).

What do computational predictors say about DIP2B p.Ser354Pro (c.1060T>C)?

AlphaMissense predicts likely benign (score 0.0375) — an in-silico prediction, not a clinical call.

DIP2B p.Ser354Pro

c.1060T>C · rs117722674 · VCV445445

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0375 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0375	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -2.87	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 3.3	GERP 0.56, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	17.3	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 0.214% European (non-Finnish) · 2,525/1,180,028 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.168% 2,714/1,614,212 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.219%	456
European (non-Finnish)grpmax	0.214%	467
Remaining individualsnot grpmax-eligible	0.115%	868
South Asian	0.0626%	1,598
Middle Eastern	0.0495%	2,021
African / African-American	0.0413%	2,421
Admixed American	0.0317%	3,159
Finnishnot grpmax-eligible	0.00625%	16,009
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser354Pro
Coding: c.1060T>C
MANE Select: NM_173602
dbSNP: rs117722674
Type: single nucleotide variant
Location: chr12:50678822 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83

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

Similar variants

DIP2B p.Asp501Val Uncertain significance ★★ ⚠ same type
DIP2B p.Cys1071Ser Uncertain significance ★★ ⚠ same type
DIP2B p.His1027Arg Uncertain significance ★★ ⚠ same type
DIP2B p.Ile681Val Uncertain significance ★★ ⚠ same type
DIP2B p.Ile968Thr Uncertain significance ★★ ⚠ same type
DIP2B p.Ile994Leu Uncertain significance ★★ ⚠ same type
DIP2B p.Pro244Ala Uncertain significance ★★ ⚠ same type
DIP2B p.Pro513Ser 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/dip2b-p-ser354pro (accessed [today's date]).

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