Is THAP11 p.Ala100Ser (c.298G>T) pathogenic?

THAP11 p.Ala100Ser (c.298G>T) is classified Uncertain significance in THAP11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-03). AlphaMissense: likely benign (0.0862); Rare (popmax 0.29%, mid).

How common is THAP11 p.Ala100Ser (c.298G>T) in the general population?

THAP11 p.Ala100Ser (c.298G>T) is rare (popmax 0.29%, mid) (gnomAD).

What do computational predictors say about THAP11 p.Ala100Ser (c.298G>T)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

THAP11 p.Ala100Ser

c.298G>T · rs754275294 · VCV2082417

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.29%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 468 bp · p 0.65 · regional, not allelic
Overall
CADD	21.0	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 0.29% Middle Eastern · 13/4,482 alleles

Filtering AF 0.172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.00406% 65/1,601,522 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.29%	345
Admixed American	0.00841%	11,897
Remaining individualsnot grpmax-eligible	0.00484%	20,675
European (non-Finnish)	0.00357%	28,041
African / African-American	0.00269%	37,125

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: THAP11
Protein: p.Ala100Ser
Coding: c.298G>T
MANE Select: NM_025082 · reported on NM_020457
dbSNP: rs754275294
Type: single nucleotide variant
Location: chr16:67842852 (GRCh38)

Full THAP11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/thap11-p-ala100ser (accessed [today's date]).

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