Is THUMPD1 p.Arg37Ser (c.109C>A) pathogenic?

THUMPD1 p.Arg37Ser (c.109C>A) is classified Uncertain significance in THUMPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.6604); Ultra-rare (popmax 0.0202%, nfe); Associated with Inborn genetic diseases.

What condition is associated with THUMPD1 p.Arg37Ser (c.109C>A)?

THUMPD1 p.Arg37Ser (c.109C>A) is associated with Inborn genetic diseases (ClinVar).

How common is THUMPD1 p.Arg37Ser (c.109C>A) in the general population?

THUMPD1 p.Arg37Ser (c.109C>A) is ultra-rare (popmax 0.0202%, nfe) (gnomAD).

What do computational predictors say about THUMPD1 p.Arg37Ser (c.109C>A)?

AlphaMissense predicts likely pathogenic (score 0.6604) — an in-silico prediction, not a clinical call.

THUMPD1 p.Arg37Ser

c.109C>A · VCV4184334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6604	likely pathogenic
REVEL	0.221	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.3	GERP -0.29, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 4,856 bp · p 0.38 · regional, not allelic
Overall
CADD	25.1	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 0.0202% European (non-Finnish) · 235/1,162,922 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.0159% 251/1,578,946 alleles · ultra-rare exomes 227/1,426,730 · genomes 24/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0202%	4,949
Remaining individualsnot grpmax-eligible	0.0164%	6,106
African / African-American	0.00674%	14,845
Admixed American	0.00183%	54,640

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: THUMPD1
Protein: p.Arg37Ser
Coding: c.109C>A
MANE Select: NM_017736
Type: single nucleotide variant
Location: chr16:20741631 (GRCh38)

Full THUMPD1 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

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/thumpd1-p-arg37ser (accessed [today's date]).

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