Is TLE2 p.Ser672Asn (c.2015G>A) pathogenic?

TLE2 p.Ser672Asn (c.2015G>A) is classified Uncertain significance in TLE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely pathogenic (0.9279); Ultra-rare (popmax 0.0513%, eas).

How common is TLE2 p.Ser672Asn (c.2015G>A) in the general population?

TLE2 p.Ser672Asn (c.2015G>A) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

What do computational predictors say about TLE2 p.Ser672Asn (c.2015G>A)?

AlphaMissense predicts likely pathogenic (score 0.9279) — an in-silico prediction, not a clinical call.

TLE2 p.Ser672Asn

c.2015G>A · rs756733503 · VCV2598489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9279 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9279	likely pathogenic
REVEL	0.234	benign-leaning
SaProt	LLR -14.57	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 31 kb · p 0.36 · regional, not allelic
Overall
CADD	27.8	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 0.0513% East Asian · 23/44,860 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00155% 25/1,613,720 alleles · ultra-rare exomes 23/1,461,382 · genomes 2/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0513%	1,950
Remaining individualsnot grpmax-eligible	0.0016%	62,464
South Asian	0.0011%	91,040

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.Ser672Asn
Coding: c.2015G>A
MANE Select: NM_003260
dbSNP: rs756733503
Type: single nucleotide variant
Location: chr19:3002385 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.40

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-ser672asn (accessed [today's date]).

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