Is TLR1 p.Ser44Pro (c.130T>C) pathogenic?

TLR1 p.Ser44Pro (c.130T>C) is classified Benign in TLR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-05-15). AlphaMissense: likely benign (0.0498); Common (popmax 7.95%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about TLR1 p.Ser44Pro (c.130T>C)?

AlphaMissense predicts likely benign (score 0.0498) — an in-silico prediction, not a clinical call.

TLR1 p.Ser44Pro

Q: How common is TLR1 p.Ser44Pro (c.130T>C) in the general population?

TLR1 p.Ser44Pro (c.130T>C) is common (popmax 7.95%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.130T>C · rs76600635 · VCV779877

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0498 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.95%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0498	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -3.17	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 -1.5
Regional constraint	o/e 1.01	unconstrained · MANE · 2,357 bp · p 0.72 · regional, not allelic
Overall
CADD	0.187	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

Grpmax group 7.95% East Asian · 3,567/44,864 alleles

Filtering AF 7.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.64%

Overall 0.282% 4,548/1,613,952 alleles · common exomes 3,943/1,461,620 · genomes 605/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	7.95%	13
Remaining individualsnot grpmax-eligible	0.711%	141
Ashkenazi Jewishnot grpmax-eligible	0.243%	411
South Asian	0.152%	660
African / African-American	0.0653%	1,532
Finnishnot grpmax-eligible	0.0593%	1,685
Middle Eastern	0.0502%	1,992
Admixed American	0.025%	4,001
European (non-Finnish)	0.0188%	5,315

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TLR1
Protein: p.Ser44Pro
Coding: c.130T>C
MANE Select: NM_003263
dbSNP: rs76600635
Type: single nucleotide variant
Location: chr4:38798702 (GRCh38)
Gene constraint: LOEUF 1.348 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.03 · 6 PDB
Residue 44: a UniProt-annotated variant site (in)

Full TLR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TLR1 p.Cys528= Benign ★★ same type
TLR1 p.Gly676= Benign/Likely benign ★★ same type
TLR1 p.His352Asn Benign ★★ same type
TLR1 p.His646= Benign ★★ same type
TLR1 p.Ile57Met Benign/Likely benign ★★ ⚠ same type
TLR1 p.Val494= Benign ★★ same type
TLR1 p.Val542Ala Benign ★★ same type
TLR1 p.Val587Gly Benign ★★ 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/tlr1-p-ser44pro (accessed [today's date]).

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