Is TELO2 p.Pro640Leu (c.1919C>T) pathogenic?

TELO2 p.Pro640Leu (c.1919C>T) is classified Uncertain significance in TELO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-20). AlphaMissense: likely benign (0.077); Very rare (popmax 0.00891%, eas).

How common is TELO2 p.Pro640Leu (c.1919C>T) in the general population?

TELO2 p.Pro640Leu (c.1919C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about TELO2 p.Pro640Leu (c.1919C>T)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

TELO2 p.Pro640Leu

c.1919C>T · rs750629442 · VCV1311211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.50	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 2	GERP 0.088, phastCons 0.006
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	12.26	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 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000558% 9/1,613,164 alleles · very rare exomes 9/1,460,812 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	8.47e-05%	1,179,999

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: TELO2
Protein: p.Pro640Leu
Coding: c.1919C>T
MANE Select: NM_016111
dbSNP: rs750629442
Type: single nucleotide variant
Location: chr16:1505486 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 640: the 'disordered' region

Full TELO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TELO2 c.2034+2T>C Likely pathogenic ★★ same type
TELO2 c.2291+1G>C Likely pathogenic ★★ same type
TELO2 p.Arg403Ter Pathogenic/Likely pathogenic ★★ same type
TELO2 p.Arg609His Pathogenic/Likely pathogenic ★★ same type
TELO2 p.Cys367Phe Pathogenic/Likely pathogenic ★★ same type
TELO2 c.830+5G>T Uncertain significance ★★ same type
TELO2 p.Ala198Val Uncertain significance ★★ ⚠ same type
TELO2 p.Ala323Pro Uncertain significance ★★ ⚠ 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/telo2-p-pro640leu (accessed [today's date]).

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