Is DAB2IP p.Thr76Met (c.227C>T) pathogenic?

DAB2IP p.Thr76Met (c.227C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely pathogenic (0.5699); Ultra-rare (popmax 0.0378%, afr).

How common is DAB2IP p.Thr76Met (c.227C>T) in the general population?

DAB2IP p.Thr76Met (c.227C>T) is ultra-rare (popmax 0.0378%, afr) (gnomAD).

What do computational predictors say about DAB2IP p.Thr76Met (c.227C>T)?

AlphaMissense predicts likely pathogenic (score 0.5699) — an in-silico prediction, not a clinical call.

DAB2IP p.Thr76Met

c.227C>T · rs368660589 · VCV2354502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5699 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0378%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5699	likely pathogenic
REVEL	0.168	moderately benign-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 105 kb · p 0.0028 · regional, not allelic
Overall
CADD	34.0	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 0.0378% African / African-American · 28/74,016 alleles

Filtering AF 0.0268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.00909% 144/1,583,342 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0378%	2,643
Middle Eastern	0.0168%	5,946
Admixed American	0.0104%	9,654
European (non-Finnish)	0.00868%	11,518
Remaining individualsnot grpmax-eligible	0.00655%	15,262
East Asian	0.00233%	43,002
South Asian	0.00228%	43,867
Finnishnot grpmax-eligible	0.00166%	60,374

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: DAB2IP
Protein: p.Thr76Met
Coding: c.227C>T
MANE Select: NM_001395010
dbSNP: rs368660589
Type: single nucleotide variant
Location: chr9:121678780 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74

Full DAB2IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAB2IP p.Ala816Thr Benign ★★ same type
DAB2IP p.Arg199= Benign ★★ same type
DAB2IP p.Arg966His Benign ★★ same type
DAB2IP p.Asp97= Benign/Likely benign ★★ same type
DAB2IP p.Lys284= Benign ★★ same type
DAB2IP p.Pro126= Likely benign ★★ same type
DAB2IP p.Ser460Leu Benign ★★ ⚠ same type
DAB2IP p.Ser68= Likely benign ★★ 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/dab2ip-p-thr76met (accessed [today's date]).

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