Is TELO2 p.Arg329His (c.986G>A) pathogenic?

TELO2 p.Arg329His (c.986G>A) is classified Uncertain significance in TELO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-18). AlphaMissense: likely benign (0.1528); Ultra-rare (popmax 0.0194%, mid); Associated with Inborn genetic diseases.

What condition is associated with TELO2 p.Arg329His (c.986G>A)?

TELO2 p.Arg329His (c.986G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TELO2 p.Arg329His (c.986G>A) in the general population?

TELO2 p.Arg329His (c.986G>A) is ultra-rare (popmax 0.0194%, mid) (gnomAD).

What do computational predictors say about TELO2 p.Arg329His (c.986G>A)?

AlphaMissense predicts likely benign (score 0.1528) — an in-silico prediction, not a clinical call.

TELO2 p.Arg329His

c.986G>A · rs370184610 · VCV2160652

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1528 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1528	likely benign
REVEL	0.642	indeterminate
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 0.77, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	26.4	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 0.0194% Middle Eastern · 1/5,150 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00143% 23/1,605,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0194%	5,150
African / African-American	0.0187%	5,346
East Asian	0.00669%	14,937
European (non-Finnish)	0.000424%	235,806

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.Arg329His
Coding: c.986G>A
MANE Select: NM_016111
dbSNP: rs370184610
Type: single nucleotide variant
Location: chr16:1500148 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TELO2 p.Arg329Cys Uncertain significance ★ ⚠ 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-arg329his (accessed [today's date]).

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