Is ASPHD2 p.Trp37Arg (c.109T>C) pathogenic?

ASPHD2 p.Trp37Arg (c.109T>C) is classified Uncertain significance in ASPHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.2658); Very rare (popmax 0.00373%, nfe).

How common is ASPHD2 p.Trp37Arg (c.109T>C) in the general population?

ASPHD2 p.Trp37Arg (c.109T>C) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about ASPHD2 p.Trp37Arg (c.109T>C)?

AlphaMissense predicts likely benign (score 0.2658) — an in-silico prediction, not a clinical call.

ASPHD2 p.Trp37Arg

c.109T>C · rs1237536853 · VCV3130452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2658	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -5.12	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 6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 548 bp · p 0.03 · regional, not allelic
Overall
CADD	24.0	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 0.00373% European (non-Finnish) · 44/1,180,044 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00279% 45/1,613,710 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,819
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: ASPHD2
Protein: p.Trp37Arg
Coding: c.109T>C
MANE Select: NM_020437
dbSNP: rs1237536853
Type: single nucleotide variant
Location: chr22:26433724 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 81.08

Full ASPHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPHD2 p.Ala47Val Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg154Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg159Gln Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg341Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg43Lys Uncertain significance ★ ⚠ same type
ASPHD2 p.Arg84Trp Uncertain significance ★ ⚠ same type
ASPHD2 p.Asn129Ser Uncertain significance ★ ⚠ same type
ASPHD2 p.Asn264Ser 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/asphd2-p-trp37arg (accessed [today's date]).

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