Is AKTIP p.Pro240Leu (c.719C>T) pathogenic?

AKTIP p.Pro240Leu (c.719C>T) is classified Uncertain significance in AKTIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: likely benign (0.1765); Ultra-rare (popmax 0.0107%, afr).

How common is AKTIP p.Pro240Leu (c.719C>T) in the general population?

AKTIP p.Pro240Leu (c.719C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about AKTIP p.Pro240Leu (c.719C>T)?

AlphaMissense predicts likely benign (score 0.1765) — an in-silico prediction, not a clinical call.

AKTIP p.Pro240Leu

c.719C>T · VCV3519309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1765 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1765	likely benign
REVEL	0.578	indeterminate
SaProt	LLR -10.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,135 bp · p 0.26 · regional, not allelic
Overall
CADD	25.9	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 0.0107% African / African-American · 8/74,902 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,613,622 alleles · ultra-rare

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: AKTIP
Protein: p.Pro240Leu
Coding: c.719C>T
MANE Select: NM_022476
Type: single nucleotide variant
Location: chr16:53492745 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 1 PDB

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

Similar variants

AKTIP p.Ala235Thr Likely benign ★★ ⚠ same type
AKTIP p.Ala47Val Uncertain significance ★ ⚠ same type
AKTIP p.Arg101His Uncertain significance ★ ⚠ same type
AKTIP p.Arg101Ser Uncertain significance ★ ⚠ same type
AKTIP p.Arg113Gln Uncertain significance ★ ⚠ same type
AKTIP p.Arg139Cys Uncertain significance ★ ⚠ same type
AKTIP p.Arg13Cys Uncertain significance ★ ⚠ same type
AKTIP p.Asp205Gly 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/aktip-p-pro240leu (accessed [today's date]).

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