Is ADAD1 p.Leu313Val (c.937C>G) pathogenic?

ADAD1 p.Leu313Val (c.937C>G) is classified Uncertain significance in ADAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely benign (0.0969); Absent from gnomAD v4.1.

How common is ADAD1 p.Leu313Val (c.937C>G) in the general population?

ADAD1 p.Leu313Val (c.937C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAD1 p.Leu313Val (c.937C>G)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

ADAD1 p.Leu313Val

c.937C>G · VCV4003532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -11.20	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 50 kb · p 0.013 · regional, not allelic
Overall
CADD	21.8	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

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: ADAD1
Protein: p.Leu313Val
Coding: c.937C>G
MANE Select: NM_139243
Type: single nucleotide variant
Location: chr4:122411310 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.19
Residue 313: the a to i editase domain

Full ADAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAD1 p.Ala183Val Uncertain significance ★ ⚠ same type
ADAD1 p.Ala352Thr Uncertain significance ★ ⚠ same type
ADAD1 p.Ala430Thr Uncertain significance ★ ⚠ same type
ADAD1 p.Ala460Thr Uncertain significance ★ ⚠ same type
ADAD1 p.Arg216Ser Uncertain significance ★ ⚠ same type
ADAD1 p.Arg279Lys Uncertain significance ★ ⚠ same type
ADAD1 p.Arg508Trp Uncertain significance ★ ⚠ same type
ADAD1 p.Arg517Gln 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/adad1-p-leu313val (accessed [today's date]).

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