Is ADAP2 p.Leu14Val (c.40C>G) pathogenic?

ADAP2 p.Leu14Val (c.40C>G) is classified Uncertain significance in ADAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.1594); Absent from gnomAD v4.1.

How common is ADAP2 p.Leu14Val (c.40C>G) in the general population?

ADAP2 p.Leu14Val (c.40C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAP2 p.Leu14Val (c.40C>G)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

ADAP2 p.Leu14Val

c.40C>G · rs1287642759 · VCV3080045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,274,126)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -7.83	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 0.91	GERP 0.26, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 36 kb · p 0.019 · regional, not allelic
Overall
CADD	23.9	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

No allele count reported in gnomAD v4.1 (AN 1,274,126). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADAP2
Protein: p.Leu14Val
Coding: c.40C>G
MANE Select: NM_018404
dbSNP: rs1287642759
Type: single nucleotide variant
Location: chr17:30922054 (GRCh38)
Gene constraint: LOEUF 1.031 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.49
Residue 14: 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-leu14val (accessed [today's date]).

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