Is TIPRL p.Asp38Asn (c.112G>A) pathogenic?

TIPRL p.Asp38Asn (c.112G>A) is classified Uncertain significance in TIPRL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely benign (0.0832); Very rare (popmax 0.00446%, eas).

How common is TIPRL p.Asp38Asn (c.112G>A) in the general population?

TIPRL p.Asp38Asn (c.112G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about TIPRL p.Asp38Asn (c.112G>A)?

AlphaMissense predicts likely benign (score 0.0832) — an in-silico prediction, not a clinical call.

TIPRL p.Asp38Asn

c.112G>A · rs752266948 · VCV2394420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0832 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0832	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 21 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	20.3	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 0.00446% East Asian · 2/44,844 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00155% 25/1,612,516 alleles · very rare exomes 24/1,460,344 · genomes 1/152,172 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,422
Remaining individualsnot grpmax-eligible	0.0032%	31,209
European (non-Finnish)	0.0017%	58,943
South Asian	0.0011%	91,008

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: TIPRL
Protein: p.Asp38Asn
Coding: c.112G>A
MANE Select: NM_152902
dbSNP: rs752266948
Type: single nucleotide variant
Location: chr1:168183909 (GRCh38)
Gene constraint: LOEUF 0.616 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 38: an α-helix

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

Similar variants

TIPRL p.Arg184Gln Uncertain significance ★ ⚠ same type
TIPRL p.Arg56Gly Uncertain significance ★ ⚠ same type
TIPRL p.Asp264Val Uncertain significance ★ ⚠ same type
TIPRL p.Gln146His Uncertain significance ★ ⚠ same type
TIPRL p.Leu125Phe Uncertain significance ★ ⚠ same type
TIPRL p.Leu231Val Uncertain significance ★ ⚠ same type
TIPRL p.Lys148Asn Uncertain significance ★ ⚠ same type
TIPRL p.Lys220Arg 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/tiprl-p-asp38asn (accessed [today's date]).

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