Is TLR7 p.Pro435Ser (c.1303C>T) pathogenic?

TLR7 p.Pro435Ser (c.1303C>T) is classified Uncertain significance in TLR7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-14). AlphaMissense: ambiguous (0.4122); Absent from gnomAD v4.1.

How common is TLR7 p.Pro435Ser (c.1303C>T) in the general population?

TLR7 p.Pro435Ser (c.1303C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TLR7 p.Pro435Ser (c.1303C>T)?

AlphaMissense predicts ambiguous (score 0.4122) — an in-silico prediction, not a clinical call.

TLR7 p.Pro435Ser

c.1303C>T · rs2518438182 · VCV2819378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4122 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4122	ambiguous
REVEL	0.128	moderately benign-leaning
SaProt	LLR -2.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 21 kb · p 1.6e-18 · regional, not allelic
Overall
CADD	20.1	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.Pro435Ser
Coding: c.1303C>T
MANE Select: NM_016562
dbSNP: rs2518438182
Type: single nucleotide variant
Location: chrX:12886811 (GRCh38)
Structure: AlphaFold pLDDT 87.60 · 1 PDB

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

Similar variants

TLR7 p.Pro435Leu Uncertain significance ★ ⚠ same residue
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
TLR7 p.Asp438Val Uncertain significance ★★ ⚠ same type
TLR7 p.Cys889Tyr Uncertain significance ★★ ⚠ same type
TLR7 p.Gln117Lys 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-pro435ser (accessed [today's date]).

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