Is DENND1B p.Ile44Val (c.130A>G) pathogenic?

DENND1B p.Ile44Val (c.130A>G) is classified Likely benign in DENND1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely benign (0.0652); Ultra-rare (popmax 0.0162%, afr).

How common is DENND1B p.Ile44Val (c.130A>G) in the general population?

DENND1B p.Ile44Val (c.130A>G) is ultra-rare (popmax 0.0162%, afr) (gnomAD).

What do computational predictors say about DENND1B p.Ile44Val (c.130A>G)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

DENND1B p.Ile44Val

c.130A>G · VCV3500898

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.37	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 1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 265 kb · p 0.094 · regional, not allelic
Overall
CADD	14.5	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 0.0162% African / African-American · 12/74,184 alleles

Filtering AF 0.0093% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00728%

Overall 0.00106% 17/1,597,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0162%	6,182
Finnishnot grpmax-eligible	0.00472%	21,178
Admixed American	0.00172%	58,284
Remaining individualsnot grpmax-eligible	0.00162%	61,770

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: DENND1B
Protein: p.Ile44Val
Coding: c.130A>G
MANE Select: NM_001195215
Type: single nucleotide variant
Location: chr1:197674166 (GRCh38)
Gene constraint: LOEUF 0.798 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.33 · 1 PDB
Residue 44: the udenn domain; an α-helix

Full DENND1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DENND1B p.Leu254= Benign ★★ same type
DENND1B p.Met597Val Benign ★★ same type
DENND1B p.Ser652= Benign ★★ same type
DENND1B p.Ala175Gly Uncertain significance ★ ⚠ same type
DENND1B p.Ala310Val Uncertain significance ★ ⚠ same type
DENND1B p.Ala327Pro Uncertain significance ★ ⚠ same type
DENND1B p.Ala394Gly Uncertain significance ★ ⚠ same type
DENND1B p.Ala394Ser 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/dennd1b-p-ile44val (accessed [today's date]).

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