Is TEAD2 p.Pro213Ser (c.637C>T) pathogenic?

TEAD2 p.Pro213Ser (c.637C>T) is classified Benign in TEAD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0697); Low-frequency (popmax 2.78%, afr).

How common is TEAD2 p.Pro213Ser (c.637C>T) in the general population?

TEAD2 p.Pro213Ser (c.637C>T) is low-frequency (popmax 2.78%, afr) (gnomAD).

What do computational predictors say about TEAD2 p.Pro213Ser (c.637C>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

TEAD2 p.Pro213Ser

c.637C>T · rs201393859 · VCV785637

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.78%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.02	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 9.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 19 kb · p 0.0002 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P209S vs ClinVar P213S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.78% African / African-American · 2,060/74,098 alleles

Filtering AF 2.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.64%

Overall 0.153% 2,441/1,600,508 alleles · low-frequency exomes 1,231/1,448,244 · genomes 1,210/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.78%	36
Admixed American	0.236%	423
Remaining individualsnot grpmax-eligible	0.21%	476
Middle Eastern	0.169%	591
South Asian	0.0134%	7,469
European (non-Finnish)	0.00775%	12,909
Finnishnot grpmax-eligible	0.00475%	21,036
East Asian	0.00224%	44,698

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: TEAD2
Protein: p.Pro213Ser
Coding: c.637C>T
MANE Select: NM_001256660
dbSNP: rs201393859
Type: single nucleotide variant
Location: chr19:49348813 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 45 PDB
Residue 209 UniProt numbering: the 'transcriptional activation' region; the 'disordered' region

Full TEAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEAD2 p.Gln116His Benign ★★ ⚠ same type
TEAD2 p.Gly226Ala Benign ★★ same type
TEAD2 p.Ala224Thr Uncertain significance ★ ⚠ same type
TEAD2 p.Ala308Val Uncertain significance ★ ⚠ same type
TEAD2 p.Ala9Val Uncertain significance ★ ⚠ same type
TEAD2 p.Arg109Pro Uncertain significance ★ ⚠ same type
TEAD2 p.Arg225Gln Uncertain significance ★ ⚠ same type
TEAD2 p.Arg225Trp 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/tead2-p-pro213ser (accessed [today's date]).

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