Is TULP1 p.Ala13Asp (c.38C>A) pathogenic?

TULP1 p.Ala13Asp (c.38C>A) is classified Uncertain significance in TULP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-13). AlphaMissense: ambiguous (0.5169); Ultra-rare (popmax 0.0517%, amr).

How common is TULP1 p.Ala13Asp (c.38C>A) in the general population?

TULP1 p.Ala13Asp (c.38C>A) is ultra-rare (popmax 0.0517%, amr) (gnomAD).

What do computational predictors say about TULP1 p.Ala13Asp (c.38C>A)?

AlphaMissense predicts ambiguous (score 0.5169) — an in-silico prediction, not a clinical call.

TULP1 p.Ala13Asp

c.38C>A · rs187701943 · VCV1054778

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5169 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0517%, amr)

Computational evidence

Protein change
AlphaMissense	0.5169	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -5.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 2, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	25.2	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 0.0517% Admixed American · 31/59,922 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00273% 44/1,612,232 alleles · ultra-rare exomes 34/1,460,654 · genomes 10/151,578 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0517%	1,933
Remaining individualsnot grpmax-eligible	0.0128%	7,805
African / African-American	0.00268%	37,254
European (non-Finnish)	0.000254%	393,219

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: TULP1
Protein: p.Ala13Asp
Coding: c.38C>A
MANE Select: NM_003322
dbSNP: rs187701943
Type: single nucleotide variant
Location: chr6:35512821 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 13: the 'disordered' region

Full TULP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TULP1 p.Ala13= Likely benign ★ same residue
TULP1 c.1112+1G>A Likely pathogenic ★★ same type
TULP1 c.1495+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.718+2T>C Pathogenic ★★ same type
TULP1 c.99+1G>A Pathogenic/Likely pathogenic ★★ same type
TULP1 c.999+5G>C Pathogenic/Likely pathogenic ★★ same type
TULP1 p.Arg311Gln Pathogenic/Likely pathogenic ★★ 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/tulp1-p-ala13asp (accessed [today's date]).

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