Is TEKT1 p.Pro7Ser (c.19C>T) pathogenic?

TEKT1 p.Pro7Ser (c.19C>T) is classified Uncertain significance in TEKT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.0813); Ultra-rare (popmax 0.0499%, mid).

How common is TEKT1 p.Pro7Ser (c.19C>T) in the general population?

TEKT1 p.Pro7Ser (c.19C>T) is ultra-rare (popmax 0.0499%, mid) (gnomAD).

What do computational predictors say about TEKT1 p.Pro7Ser (c.19C>T)?

AlphaMissense predicts likely benign (score 0.0813) — an in-silico prediction, not a clinical call.

TEKT1 p.Pro7Ser

c.19C>T · VCV3454704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0813 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0499%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0813	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.46	GERP -2.4
Regional constraint	o/e 0.95	unconstrained · MANE · 30 kb · p 0.24 · regional, not allelic
Overall
CADD	3.176	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 0.0499% Middle Eastern · 3/6,008 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00724%

Overall 0.00744% 118/1,586,664 alleles · ultra-rare exomes 107/1,434,446 · genomes 11/152,218 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0499%	2,003
European (non-Finnish)	0.00853%	11,728
Remaining individualsnot grpmax-eligible	0.00816%	12,261
African / African-American	0.00683%	14,640
Finnishnot grpmax-eligible	0.0047%	21,296
Admixed American	0.00395%	25,298

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: TEKT1
Protein: p.Pro7Ser
Coding: c.19C>T
MANE Select: NM_053285
Type: single nucleotide variant
Location: chr17:6830358 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.16 · 2 PDB

Full TEKT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TEKT1 p.Ala140Ser Uncertain significance ★ ⚠ same type
TEKT1 p.Ala204Thr Uncertain significance ★ ⚠ same type
TEKT1 p.Ala240Val Uncertain significance ★ ⚠ same type
TEKT1 p.Ala333Thr Uncertain significance ★ ⚠ same type
TEKT1 p.Ala349Thr Uncertain significance ★ ⚠ same type
TEKT1 p.Arg122Cys Uncertain significance ★ same type
TEKT1 p.Arg122His Uncertain significance ★ same type
TEKT1 p.Arg152Cys 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/tekt1-p-pro7ser (accessed [today's date]).

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