Is TECPR2 p.Met1398Val (c.4192A>G) pathogenic?

TECPR2 p.Met1398Val (c.4192A>G) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.0586); Very rare (popmax 0.00364%, nfe).

How common is TECPR2 p.Met1398Val (c.4192A>G) in the general population?

TECPR2 p.Met1398Val (c.4192A>G) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about TECPR2 p.Met1398Val (c.4192A>G)?

AlphaMissense predicts likely benign (score 0.0586) — an in-silico prediction, not a clinical call.

TECPR2 p.Met1398Val

c.4192A>G · rs751255793 · VCV2579334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0586 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0586	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -4.46	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 -5.4	GERP -2.6
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	0.004	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 0.00364% European (non-Finnish) · 43/1,179,972 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00274% 44/1,607,610 alleles · very rare exomes 43/1,455,400 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,441
Remaining individualsnot grpmax-eligible	0.0016%	62,440

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.Met1398Val
Coding: c.4192A>G
MANE Select: NM_014844
dbSNP: rs751255793
Type: single nucleotide variant
Location: chr14:102498213 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27
Residue 1398: the 'disordered' region

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

Similar variants

TECPR2 p.Met1398Arg Uncertain significance ★ ⚠ same residue
TECPR2 p.Met1398Ile Uncertain significance ★ ⚠ 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-met1398val (accessed [today's date]).

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