Is TECPR2 p.Asn548Ser (c.1643A>G) pathogenic?

TECPR2 p.Asn548Ser (c.1643A>G) is classified Conflicting classifications of pathogenicity in TECPR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-10-29). AlphaMissense: likely benign (0.0467); Ultra-rare (popmax 0.0145%, amr); Associated with Inborn genetic diseases.

What condition is associated with TECPR2 p.Asn548Ser (c.1643A>G)?

TECPR2 p.Asn548Ser (c.1643A>G) is associated with Inborn genetic diseases, hereditary spastic paraplegia 49, hereditary spastic paraplegia (ClinVar).

How common is TECPR2 p.Asn548Ser (c.1643A>G) in the general population?

TECPR2 p.Asn548Ser (c.1643A>G) is ultra-rare (popmax 0.0145%, amr) (gnomAD).

What do computational predictors say about TECPR2 p.Asn548Ser (c.1643A>G)?

AlphaMissense predicts likely benign (score 0.0467) — an in-silico prediction, not a clinical call.

TECPR2 p.Asn548Ser

c.1643A>G · rs904496072 · VCV989669

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0467 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0467	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -4.13	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 6.6	GERP 0.72, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	4.267	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

Grpmax group 0.0145% Admixed American · 7/48,294 alleles

Filtering AF 0.0067% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00475%

Overall 0.000518% 8/1,545,164 alleles · ultra-rare exomes 6/1,392,966 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0145%	6,899
East Asian	0.00225%	44,402

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.Asn548Ser
Coding: c.1643A>G
MANE Select: NM_014844
dbSNP: rs904496072
Type: single nucleotide variant
Location: chr14:102434460 (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

Also linked: hereditary spastic paraplegia 49 hereditary spastic paraplegia

Similar variants

TECPR2 p.Asn548Lys Likely benign ★★ same residue
TECPR2 c.1084+2T>C Likely pathogenic ★★ same condition
TECPR2 c.1418-2A>G Likely pathogenic ★★ same condition
TECPR2 c.2753-1G>A Likely pathogenic ★★ same condition
TECPR2 p.Gln1189Ter Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln191Ter Pathogenic/Likely pathogenic ★★ same condition
TECPR2 p.Gln852Ter Pathogenic ★★ same condition
TECPR2 p.Trp1024Ter Pathogenic ★★ 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-asn548ser (accessed [today's date]).

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