Is ADTRP p.Lys35Arg (c.104A>G) pathogenic?

ADTRP p.Lys35Arg (c.104A>G) is classified Uncertain significance in ADTRP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). AlphaMissense: likely benign (0.0751); Absent from gnomAD v4.1.

How common is ADTRP p.Lys35Arg (c.104A>G) in the general population?

ADTRP p.Lys35Arg (c.104A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADTRP p.Lys35Arg (c.104A>G)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

ADTRP p.Lys35Arg

c.104A>G · VCV4839620

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.30	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 -0.18	GERP -4.1
Regional constraint	o/e 0.91	unconstrained · MANE · 64 kb · p 0.15 · regional, not allelic
Overall
CADD	1.226	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: ADTRP
Protein: p.Lys35Arg
Coding: c.104A>G
MANE Select: NM_032744
Type: single nucleotide variant
Location: chr6:11778656 (GRCh38)
Gene constraint: LOEUF 1.074 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.99

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

Similar variants

ADTRP c.154-1655T>C Uncertain significance ★ same type
ADTRP c.154-1691G>A Uncertain significance ★ same type
ADTRP c.154-1692A>G Uncertain significance ★ same type
ADTRP p.Ala205Thr Uncertain significance ★ ⚠ same type
ADTRP p.Arg145Thr Uncertain significance ★ ⚠ same type
ADTRP p.Arg169Cys Uncertain significance ★ ⚠ same type
ADTRP p.Arg169Ser Uncertain significance ★ ⚠ same type
ADTRP p.Arg226Trp 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/adtrp-p-lys35arg (accessed [today's date]).

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