Is TELO2 p.Arg607Trp (c.1819C>T) pathogenic?

TELO2 p.Arg607Trp (c.1819C>T) is classified Likely benign in TELO2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1382); Rare (popmax 0.227%, sas).

How common is TELO2 p.Arg607Trp (c.1819C>T) in the general population?

TELO2 p.Arg607Trp (c.1819C>T) is rare (popmax 0.227%, sas) (gnomAD).

What do computational predictors say about TELO2 p.Arg607Trp (c.1819C>T)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

TELO2 p.Arg607Trp

c.1819C>T · rs146401595 · VCV722324

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 1.2, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	29.2	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 0.227% South Asian · 207/91,090 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.192%

Overall 0.129% 2,086/1,611,104 alleles · rare exomes 1,930/1,458,740 · genomes 156/152,364 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.311%	321
South Asiangrpmax	0.227%	440
Amishnot grpmax-eligible	0.219%	456
Remaining individualsnot grpmax-eligible	0.154%	651
European (non-Finnish)	0.132%	758
Middle Eastern	0.0825%	1,212
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
African / African-American	0.02%	5,004
East Asian	0.00446%	22,440
Admixed American	0.00333%	30,015

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg607Trp
Coding: c.1819C>T
MANE Select: NM_016111
dbSNP: rs146401595
Type: single nucleotide variant
Location: chr16:1502979 (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

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-arg607trp (accessed [today's date]).

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