Is TELO2 p.Val193Ala (c.578T>C) pathogenic?

TELO2 p.Val193Ala (c.578T>C) is classified Benign in TELO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1612); Low-frequency (popmax 1.91%, sas).

How common is TELO2 p.Val193Ala (c.578T>C) in the general population?

TELO2 p.Val193Ala (c.578T>C) is low-frequency (popmax 1.91%, sas) (gnomAD).

What do computational predictors say about TELO2 p.Val193Ala (c.578T>C)?

AlphaMissense predicts likely benign (score 0.1612) — an in-silico prediction, not a clinical call.

TELO2 p.Val193Ala

c.578T>C · rs141647559 · VCV791371

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1612 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1612	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.58	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 1.9	GERP 0.29, phastCons 0.026
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.22 · regional, not allelic
Overall
CADD	12.6	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 1.91% South Asian · 1,740/90,946 alleles

Filtering AF 1.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.81%

Overall 0.446% 7,167/1,607,042 alleles · low-frequency exomes 6,628/1,454,688 · genomes 539/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.91%	52
Ashkenazi Jewishnot grpmax-eligible	1.69%	59
Middle Eastern	1.48%	68
Remaining individualsnot grpmax-eligible	0.501%	199
European (non-Finnish)	0.362%	276
Admixed American	0.292%	342
Finnishnot grpmax-eligible	0.0887%	1,127
African / African-American	0.0533%	1,875
East Asian	0.00672%	14,891

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.Val193Ala
Coding: c.578T>C
MANE Select: NM_016111
dbSNP: rs141647559
Type: single nucleotide variant
Location: chr16:1495588 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.74 · 4 PDB
Residue 193: an α-helix

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

Similar variants

TELO2 p.Val193= Likely benign ★ same residue
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

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-val193ala (accessed [today's date]).

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