Is DIP2A p.Ala86Thr (c.256G>A) pathogenic?

DIP2A p.Ala86Thr (c.256G>A) is classified Likely benign in DIP2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.0625); Ultra-rare (popmax 0.0322%, afr).

How common is DIP2A p.Ala86Thr (c.256G>A) in the general population?

DIP2A p.Ala86Thr (c.256G>A) is ultra-rare (popmax 0.0322%, afr) (gnomAD).

What do computational predictors say about DIP2A p.Ala86Thr (c.256G>A)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

DIP2A p.Ala86Thr

c.256G>A · rs781249841 · VCV2516500

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0322%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.51	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 3.9	GERP -1.9, phastCons 0.97
Regional constraint	o/e 0.85	unconstrained · MANE · 108 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	9.339	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 0.0322% African / African-American · 24/74,426 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00284% 45/1,585,824 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0322%	3,101
Admixed American	0.00542%	18,449
European (non-Finnish)	0.00154%	64,791

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: DIP2A
Protein: p.Ala86Thr
Coding: c.256G>A
MANE Select: NM_015151
dbSNP: rs781249841
Type: single nucleotide variant
Location: chr21:46490692 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93
Residue 86: the dmap1-binding domain; the 'disordered' region

Full DIP2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIP2A p.Ala676Thr Uncertain significance ★★ ⚠ same type
DIP2A p.Glu832Lys Uncertain significance ★★ ⚠ same type
DIP2A p.Pro333= Benign ★★ same type
DIP2A p.Pro798Leu Benign/Likely benign ★★ ⚠ same type
DIP2A p.Thr848= Benign/Likely benign ★★ same type
DIP2A p.Val1531= Benign ★★ same type
DIP2A c.1429+2T>G Likely pathogenic ★ same type
DIP2A c.2395-2A>G 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/dip2a-p-ala86thr (accessed [today's date]).

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