Is TECPR2 p.Leu195Pro (c.584T>C) pathogenic?

TECPR2 p.Leu195Pro (c.584T>C) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely pathogenic (0.99); Absent from gnomAD v4.1.

How common is TECPR2 p.Leu195Pro (c.584T>C) in the general population?

TECPR2 p.Leu195Pro (c.584T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TECPR2 p.Leu195Pro (c.584T>C)?

AlphaMissense predicts likely pathogenic (score 0.99) — an in-silico prediction, not a clinical call.

TECPR2 p.Leu195Pro

c.584T>C · rs2139702960 · VCV1313262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.99 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.99	likely pathogenic · top 2% in TECPR2
REVEL	0.689	pathogenic-leaning
SaProt	LLR -15.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TECPR2
Protein: p.Leu195Pro
Coding: c.584T>C
MANE Select: NM_014844
dbSNP: rs2139702960
Type: single nucleotide variant
Location: chr14:102414739 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27

Full TECPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TECPR2 p.Leu195Phe Uncertain significance ★ ⚠ same residue
TECPR2 p.Leu195= Likely benign ★ same residue
TECPR2 c.1084+2T>C Likely pathogenic ★★ same type
TECPR2 c.1418-2A>G Likely pathogenic ★★ same type
TECPR2 c.2753-1G>A Likely pathogenic ★★ same type
TECPR2 p.Gln1189Ter Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Gln191Ter Pathogenic/Likely pathogenic ★★ same type
TECPR2 p.Gln852Ter Pathogenic ★★ 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/tecpr2-p-leu195pro (accessed [today's date]).

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