Is TELO2 p.Ala240Val (c.719C>T) pathogenic?

TELO2 p.Ala240Val (c.719C>T) is classified Likely benign in TELO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). AlphaMissense: likely benign (0.0721); Ultra-rare (popmax 0.0176%, mid); Associated with Inborn genetic diseases.

What condition is associated with TELO2 p.Ala240Val (c.719C>T)?

TELO2 p.Ala240Val (c.719C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TELO2 p.Ala240Val (c.719C>T) in the general population?

TELO2 p.Ala240Val (c.719C>T) is ultra-rare (popmax 0.0176%, mid) (gnomAD).

What do computational predictors say about TELO2 p.Ala240Val (c.719C>T)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

TELO2 p.Ala240Val

c.719C>T · VCV3454769

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -7.97	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 -8	GERP -3.7
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	0.073	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 0.0176% Middle Eastern · 1/5,682 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.00239% 37/1,550,578 alleles · ultra-rare exomes 31/1,398,340 · genomes 6/152,238 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0176%	5,682
African / African-American	0.00684%	14,617
Remaining individualsnot grpmax-eligible	0.00333%	30,026
South Asian	0.00238%	42,015
European (non-Finnish)	0.00235%	42,496

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.Ala240Val
Coding: c.719C>T
MANE Select: NM_016111
Type: single nucleotide variant
Location: chr16:1497397 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 240: an α-helix

Full TELO2 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

Similar variants

TELO2 p.Ala240= Likely benign ★★ same residue
TELO2 p.Ala198Val Uncertain significance ★★ ⚠ same condition
TELO2 p.Ala511Ser Uncertain significance ★★ ⚠ same condition
TELO2 p.Ala658Val Uncertain significance ★★ ⚠ same condition
TELO2 p.Ala744Thr Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg122Trp Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg129Cys Uncertain significance ★★ ⚠ same condition
TELO2 p.Arg194Trp Uncertain significance ★★ ⚠ 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/telo2-p-ala240val (accessed [today's date]).

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