Is TECPR2 p.Ser506Leu (c.1517C>T) pathogenic?

TECPR2 p.Ser506Leu (c.1517C>T) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). AlphaMissense: likely benign (0.1021); Very rare (popmax 0.00166%, sas).

How common is TECPR2 p.Ser506Leu (c.1517C>T) in the general population?

TECPR2 p.Ser506Leu (c.1517C>T) is very rare (popmax 0.00166%, sas) (gnomAD).

What do computational predictors say about TECPR2 p.Ser506Leu (c.1517C>T)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

TECPR2 p.Ser506Leu

c.1517C>T · VCV3902673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00166%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.12	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 6	GERP 0.72, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	25.3	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 0.00166% South Asian · 1/60,344 alleles

Filtering AF 7.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000273% 4/1,464,782 alleles · very rare exomes 4/1,312,502 · genomes 0/152,280 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00166%	60,344
European (non-Finnish)	0.000271%	368,382

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.Ser506Leu
Coding: c.1517C>T
MANE Select: NM_014844
Type: single nucleotide variant
Location: chr14:102434334 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 506: the 'disordered' region

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

Similar variants

TECPR2 p.Ser506= 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
TECPR2 p.Trp1024Ter 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-ser506leu (accessed [today's date]).

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