Is TELO2 p.Val723Phe (c.2167G>T) pathogenic?

TELO2 p.Val723Phe (c.2167G>T) is classified Uncertain significance in TELO2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: ambiguous (0.5297); Absent from gnomAD v4.1; Associated with microcephaly.

What condition is associated with TELO2 p.Val723Phe (c.2167G>T)?

TELO2 p.Val723Phe (c.2167G>T) is associated with microcephaly (ClinVar).

How common is TELO2 p.Val723Phe (c.2167G>T) in the general population?

TELO2 p.Val723Phe (c.2167G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TELO2 p.Val723Phe (c.2167G>T)?

AlphaMissense predicts ambiguous (score 0.5297) — an in-silico prediction, not a clinical call.

TELO2 p.Val723Phe

c.2167G>T · rs1207905439 · VCV813678

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5297 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

microcephaly

Computational evidence

Protein change
AlphaMissense	0.5297	ambiguous
REVEL	0.498	indeterminate
SaProt	LLR -8.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TELO2
Protein: p.Val723Phe
Coding: c.2167G>T
MANE Select: NM_016111
dbSNP: rs1207905439
Type: single nucleotide variant
Location: chr16:1506992 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB

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

Disease context

microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-val723phe (accessed [today's date]).

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