Is DENND11 p.Ala7Val (c.20C>T) pathogenic?

DENND11 p.Ala7Val (c.20C>T) is classified Uncertain significance in DENND11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.2649); Very rare (popmax 0.000603%, nfe).

How common is DENND11 p.Ala7Val (c.20C>T) in the general population?

DENND11 p.Ala7Val (c.20C>T) is very rare (popmax 0.000603%, nfe) (gnomAD).

What do computational predictors say about DENND11 p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.2649) — an in-silico prediction, not a clinical call.

DENND11 p.Ala7Val

c.20C>T · rs2485578625 · VCV3081428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000603%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2649	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.60	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 4.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 39 kb · p 9.9e-06 · regional, not allelic
Overall
CADD	24.3	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 0.000603% European (non-Finnish) · 5/829,848 alleles

Filtering AF 0.000177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000128%

Overall 0.000598% 5/836,312 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: DENND11
Protein: p.Ala7Val
Coding: c.20C>T
MANE Select: NM_001080392
dbSNP: rs2485578625
Type: single nucleotide variant
Location: chr7:141702134 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.87
Residue 7: the 'disordered' region

Full DENND11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DENND11 p.Ala149Thr Uncertain significance ★★ ⚠ same type
DENND11 p.Asp345Asn Uncertain significance ★★ ⚠ same type
DENND11 p.Ala14Val Uncertain significance ★ ⚠ same type
DENND11 p.Ala253Val Uncertain significance ★ ⚠ same type
DENND11 p.Ala29Thr Uncertain significance ★ ⚠ same type
DENND11 p.Ala29Val Uncertain significance ★ ⚠ same type
DENND11 p.Ala317Val Uncertain significance ★ ⚠ same type
DENND11 p.Ala409Thr 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/dennd11-p-ala7val (accessed [today's date]).

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