Is TULP1 p.Pro143Ala (c.427C>G) pathogenic?

TULP1 p.Pro143Ala (c.427C>G) is classified Likely benign in TULP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.0585); Rare (popmax 0.259%, afr).

How common is TULP1 p.Pro143Ala (c.427C>G) in the general population?

TULP1 p.Pro143Ala (c.427C>G) is rare (popmax 0.259%, afr) (gnomAD).

What do computational predictors say about TULP1 p.Pro143Ala (c.427C>G)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

TULP1 p.Pro143Ala

c.427C>G · rs114056023 · VCV707591

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.259%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.42	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 1.2	GERP -3.1, phastCons 0.97
Regional constraint	o/e 1.05	unconstrained · MANE · 3,598 bp · p 0.36 · regional, not allelic
Overall
CADD	14.64	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 0.259% African / African-American · 194/74,964 alleles

Filtering AF 0.229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.218%

Overall 0.0143% 231/1,613,538 alleles · rare exomes 124/1,461,474 · genomes 107/152,064 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.259%	386
Middle Eastern	0.0825%	1,212
Admixed American	0.0233%	4,287
Remaining individualsnot grpmax-eligible	0.0224%	4,464
South Asian	0.0022%	45,535
European (non-Finnish)	0.000169%	589,984

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.Pro143Ala
Coding: c.427C>G
MANE Select: NM_003322
dbSNP: rs114056023
Type: single nucleotide variant
Location: chr6:35510933 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 143: the 'disordered' region

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

Similar variants

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
TULP1 p.Arg311Trp 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-pro143ala (accessed [today's date]).

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