Is TLR7 p.Val795Phe (c.2383G>T) pathogenic?

TLR7 p.Val795Phe (c.2383G>T) is classified Pathogenic in TLR7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-09-16). AlphaMissense: ambiguous (0.4632); Absent from gnomAD v4.1; Associated with immunodeficiency 74, COVID-19-related, X-linked.

What condition is associated with TLR7 p.Val795Phe (c.2383G>T)?

TLR7 p.Val795Phe (c.2383G>T) is associated with immunodeficiency 74, COVID-19-related, X-linked (ClinVar).

How common is TLR7 p.Val795Phe (c.2383G>T) in the general population?

TLR7 p.Val795Phe (c.2383G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TLR7 p.Val795Phe (c.2383G>T)?

AlphaMissense predicts ambiguous (score 0.4632) — an in-silico prediction, not a clinical call.

TLR7 p.Val795Phe

c.2383G>T · rs200553089 · VCV977233

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency 74, COVID-19-related, X-linked

Computational evidence

Protein change
AlphaMissense	0.4632	ambiguous
REVEL	0.375	indeterminate
SaProt	LLR -6.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.27, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 21 kb · p 1.6e-18 · regional, not allelic
Overall
CADD	22.7	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: TLR7
Protein: p.Val795Phe
Coding: c.2383G>T
MANE Select: NM_016562
dbSNP: rs200553089
Type: single nucleotide variant
Location: chrX:12887891 (GRCh38)
Structure: AlphaFold pLDDT 87.60 · 1 PDB
Residue 795: a UniProt-annotated variant site (in imd74; no enhanced expression after stimulation by imiquimod; defective up-regulation of type i ifn-related genes; decreased expression of ifng)

Full TLR7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 74, COVID-19-related, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TLR7 p.Lys315Gln Uncertain significance ★★ ⚠ same condition
TLR7 p.Asp548Ala Uncertain significance ★ ⚠ same condition
TLR7 p.Asp332fs Likely pathogenic ★ same condition
TLR7 p.Gln710fs Pathogenic same condition
TLR7 p.Arg357Cys Uncertain significance ★★ ⚠ same type
TLR7 p.Asn159Asp Uncertain significance ★★ ⚠ same type
TLR7 p.Asn720Ser Uncertain significance ★★ ⚠ same type
TLR7 p.Asp198Gly 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/tlr7-p-val795phe (accessed [today's date]).

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