Is ADAP2 p.Leu131Phe (c.391C>T) pathogenic?

ADAP2 p.Leu131Phe (c.391C>T) is classified Uncertain significance in ADAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.0731); Absent from gnomAD v4.1.

How common is ADAP2 p.Leu131Phe (c.391C>T) in the general population?

ADAP2 p.Leu131Phe (c.391C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAP2 p.Leu131Phe (c.391C>T)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

ADAP2 p.Leu131Phe

c.391C>T · VCV4010925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.00	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 -0.35	GERP -1.7
Regional constraint	o/e 0.89	unconstrained · MANE · 36 kb · p 0.019 · regional, not allelic
Overall
CADD	4.118	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADAP2
Protein: p.Leu131Phe
Coding: c.391C>T
MANE Select: NM_018404
Type: single nucleotide variant
Location: chr17:30931962 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.49
Residue 131: the arf-gap domain

Full ADAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAP2 p.Ala279Thr Uncertain significance ★ ⚠ same type
ADAP2 p.Ala36Ser Uncertain significance ★ ⚠ same type
ADAP2 p.Arg16Gly Uncertain significance ★ ⚠ same type
ADAP2 p.Arg209Lys Uncertain significance ★ ⚠ same type
ADAP2 p.Arg229His Uncertain significance ★ ⚠ same type
ADAP2 p.Arg254Lys Uncertain significance ★ ⚠ same type
ADAP2 p.Arg285Gln Uncertain significance ★ ⚠ same type
ADAP2 p.Arg322Gln 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/adap2-p-leu131phe (accessed [today's date]).

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