Is CHTOP p.Thr33Met (c.98C>T) pathogenic?

CHTOP p.Thr33Met (c.98C>T) is classified Likely benign in CHTOP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.0386); Ultra-rare (popmax 0.0165%, mid).

How common is CHTOP p.Thr33Met (c.98C>T) in the general population?

CHTOP p.Thr33Met (c.98C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CHTOP p.Thr33Met (c.98C>T)?

AlphaMissense predicts likely benign (score 0.0386) — an in-silico prediction, not a clinical call.

CHTOP p.Thr33Met

c.98C>T · rs770553662 · VCV2364505

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0386 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0386	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -7.28	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 5.1	GERP 0.67, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 5,699 bp · p 0.00058 · regional, not allelic
Overall
CADD	19.51	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000547% 8/1,461,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00167%	60,024
South Asian	0.0011%	91,086
European (non-Finnish)	0.000424%	236,006

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: CHTOP
Protein: p.Thr33Met
Coding: c.98C>T
MANE Select: NM_015607
dbSNP: rs770553662
Type: single nucleotide variant
Location: chr1:153638327 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.64
Residue 33: a modified residue (phosphothreonine)

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

Similar variants

CHTOP p.Ala99Ser Uncertain significance ★ ⚠ same type
CHTOP p.Arg110Lys Uncertain significance ★ ⚠ same type
CHTOP p.Arg124Thr Uncertain significance ★ ⚠ same type
CHTOP p.Arg157Gln Uncertain significance ★ ⚠ same type
CHTOP p.Arg159His Uncertain significance ★ ⚠ same type
CHTOP p.Arg169His Uncertain significance ★ ⚠ same type
CHTOP p.Arg187Trp Uncertain significance ★ ⚠ same type
CHTOP p.Arg195Leu 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/chtop-p-thr33met (accessed [today's date]).

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