Is TECPR2 p.Arg273Cys (c.817C>T) pathogenic?

TECPR2 p.Arg273Cys (c.817C>T) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely benign (0.1573); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with TECPR2 p.Arg273Cys (c.817C>T)?

TECPR2 p.Arg273Cys (c.817C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TECPR2 p.Arg273Cys (c.817C>T) in the general population?

TECPR2 p.Arg273Cys (c.817C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about TECPR2 p.Arg273Cys (c.817C>T)?

AlphaMissense predicts likely benign (score 0.1573) — an in-silico prediction, not a clinical call.

TECPR2 p.Arg273Cys

c.817C>T · VCV3325206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1573 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1573	likely benign
REVEL	0.353	indeterminate
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.61, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	27.8	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 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00105% 17/1,613,992 alleles · very rare exomes 15/1,461,890 · genomes 2/152,102 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
African / African-American	0.00267%	37,434
East Asian	0.00223%	44,898
European (non-Finnish)	0.00102%	98,336

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: TECPR2
Protein: p.Arg273Cys
Coding: c.817C>T
MANE Select: NM_014844
Type: single nucleotide variant
Location: chr14:102425157 (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.Arg273His Uncertain significance ★★ ⚠ 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.Arg32His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg716His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg943Trp Uncertain significance ★★ ⚠ same condition
TECPR2 p.Asp1021Asn 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-arg273cys (accessed [today's date]).

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