Is TLR2 p.Ala26Val (c.77C>T) pathogenic?

TLR2 p.Ala26Val (c.77C>T) is classified Likely benign in TLR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-02). AlphaMissense: likely benign (0.0819); Rare (popmax 0.224%, afr); Associated with TLR2-related disorder.

What condition is associated with TLR2 p.Ala26Val (c.77C>T)?

TLR2 p.Ala26Val (c.77C>T) is associated with TLR2-related disorder (ClinVar).

How common is TLR2 p.Ala26Val (c.77C>T) in the general population?

TLR2 p.Ala26Val (c.77C>T) is rare (popmax 0.224%, afr) (gnomAD).

What do computational predictors say about TLR2 p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

TLR2 p.Ala26Val

c.77C>T · rs145391095 · VCV3041199

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.224%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TLR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -5.80	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 -1.2	GERP -2.3
Regional constraint	o/e 0.90	unconstrained · MANE · 2,351 bp · p 0.0021 · regional, not allelic
Overall
CADD	0.421	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 0.224% African / African-American · 168/75,022 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.186%

Overall 0.0113% 182/1,614,078 alleles · rare exomes 95/1,461,872 · genomes 87/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.224%	447
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00333%	30,000
South Asian	0.00329%	30,357
European (non-Finnish)	8.47e-05%	1,179,999

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: TLR2
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_001318789
dbSNP: rs145391095
Type: single nucleotide variant
Location: chr4:153702984 (GRCh38)
Gene constraint: LOEUF 1.432 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.87 · 7 PDB

Full TLR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TLR2-related disorder

Similar variants

TLR2 p.Ala400= Benign same condition
TLR2 p.Asn729Ser Benign same condition
TLR2 p.Leu563= Benign same condition
TLR2 p.Leu81Pro Likely benign same condition
TLR2 p.Phe707= Benign same condition
TLR2 p.Pro456= Likely benign same condition
TLR2 p.Thr411Ile Benign same condition
TLR2 p.Thr65= Likely benign same condition

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/tlr2-p-ala26val (accessed [today's date]).

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