Is TLE2 p.Ser182Pro (c.544T>C) pathogenic?

TLE2 p.Ser182Pro (c.544T>C) is classified Uncertain significance in TLE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.052); Very rare (popmax 0.00354%, amr).

How common is TLE2 p.Ser182Pro (c.544T>C) in the general population?

TLE2 p.Ser182Pro (c.544T>C) is very rare (popmax 0.00354%, amr) (gnomAD).

What do computational predictors say about TLE2 p.Ser182Pro (c.544T>C)?

AlphaMissense predicts likely benign (score 0.052) — an in-silico prediction, not a clinical call.

TLE2 p.Ser182Pro

c.544T>C · rs1291686620 · VCV2350371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00354%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.052	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.22	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 -0.27
Regional constraint	o/e 1.03	unconstrained · MANE · 31 kb · p 0.36 · regional, not allelic
Overall
CADD	6.953	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

Grpmax group 0.00354% Admixed American · 2/56,428 alleles

Filtering AF 0.000588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00022%

Overall 0.000635% 10/1,573,922 alleles · very rare exomes 7/1,422,192 · genomes 3/151,730 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00354%	28,214
African / African-American	0.00271%	36,962
Remaining individualsnot grpmax-eligible	0.00163%	61,320
European (non-Finnish)	0.000428%	233,723

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: TLE2
Protein: p.Ser182Pro
Coding: c.544T>C
MANE Select: NM_003260
dbSNP: rs1291686620
Type: single nucleotide variant
Location: chr19:3019289 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.40
Residue 182: the 'gp domain' region; the 'disordered' region

Full TLE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TLE2 p.Ala110Thr Uncertain significance ★ ⚠ same type
TLE2 p.Ala133Val Uncertain significance ★ ⚠ same type
TLE2 p.Ala164Val Uncertain significance ★ ⚠ same type
TLE2 p.Ala167Val Uncertain significance ★ ⚠ same type
TLE2 p.Ala168Val Uncertain significance ★ ⚠ same type
TLE2 p.Ala187Ser Uncertain significance ★ ⚠ same type
TLE2 p.Ala187Val Uncertain significance ★ ⚠ same type
TLE2 p.Ala192Val 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/tle2-p-ser182pro (accessed [today's date]).

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