Is TERF2 p.Lys447= (c.1341A>G) pathogenic?

TERF2 p.Lys447= (c.1341A>G) is classified Likely benign in TERF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). Very rare (popmax 0.00051%, nfe).

How common is TERF2 p.Lys447= (c.1341A>G) in the general population?

TERF2 p.Lys447= (c.1341A>G) is very rare (popmax 0.00051%, nfe) (gnomAD).

TERF2 p.Lys447=

c.1341A>G · rs2543389736 · VCV3176157

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 2, phastCons 1
Overall
CADD	10.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00051% European (non-Finnish) · 6/1,176,248 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000373% 6/1,609,972 alleles · very rare exomes 6/1,457,676 · genomes 0/152,296 · joint denominator

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: TERF2
Protein: p.Lys447=
Coding: c.1341A>G
MANE Select: NM_005652
dbSNP: rs2543389736
Type: single nucleotide variant
Location: chr16:69361489 (GRCh38)
Gene constraint: LOEUF 0.444 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.36 · 18 PDB
Residue 447: the 'disordered' region

Full TERF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TERF2 c.1341-42T>C Benign ★★ same type
TERF2 c.1426+95C>T Benign ★★ same type
TERF2 c.380-5C>T Benign ★★ same type
TERF2 c.840+145C>T Benign ★★ same type
TERF2 c.947+27G>A Benign ★★ same type
TERF2 c.*142G>A Benign ★★ same type
TERF2 c.*159C>T Benign ★★ same type
TERF2 c.*220A>G Benign ★★ 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/terf2-p-lys447 (accessed [today's date]).

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