Is TECPR2 p.Leu195Phe (c.583C>T) pathogenic?

TECPR2 p.Leu195Phe (c.583C>T) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely pathogenic (0.5942); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TECPR2 p.Leu195Phe (c.583C>T)?

TECPR2 p.Leu195Phe (c.583C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TECPR2 p.Leu195Phe (c.583C>T) in the general population?

TECPR2 p.Leu195Phe (c.583C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TECPR2 p.Leu195Phe (c.583C>T)?

AlphaMissense predicts likely pathogenic (score 0.5942) — an in-silico prediction, not a clinical call.

TECPR2 p.Leu195Phe

c.583C>T · VCV3805405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5942 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5942	likely pathogenic
REVEL	0.181	moderately benign-leaning
SaProt	LLR -12.66	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	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	25.0	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

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.Leu195Phe
Coding: c.583C>T
MANE Select: NM_014844
Type: single nucleotide variant
Location: chr14:102414738 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TECPR2 p.Leu195Pro Uncertain significance ★ ⚠ same residue
TECPR2 p.Leu195= Likely benign ★ same residue
TECPR2 p.Ala1176Thr Uncertain significance ★★ ⚠ same condition
TECPR2 p.Ala380Val Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg1066Cys Uncertain significance ★★ same condition
TECPR2 p.Arg273His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg32His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg716His Uncertain significance ★★ ⚠ same condition

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-leu195phe (accessed [today's date]).

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