Is AKTIP p.Val121Ile (c.361G>A) pathogenic?

AKTIP p.Val121Ile (c.361G>A) is classified Uncertain significance in AKTIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.1439); Very rare (popmax 0.00668%, eas).

How common is AKTIP p.Val121Ile (c.361G>A) in the general population?

AKTIP p.Val121Ile (c.361G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about AKTIP p.Val121Ile (c.361G>A)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

AKTIP p.Val121Ile

c.361G>A · VCV3519301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.82	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 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.15	constrained · MANE · 59 bp · p 1.1e-05 · regional, not allelic
Overall
CADD	23.6	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 0.00668% East Asian · 3/44,890 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00124% 20/1,614,182 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
South Asian	0.00329%	30,361
African / African-American	0.00133%	75,038
European (non-Finnish)	0.0011%	90,771

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.Val121Ile
Coding: c.361G>A
MANE Select: NM_022476
Type: single nucleotide variant
Location: chr16:53495126 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 1 PDB
Residue 121: the ubc core domain; a β-strand

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-val121ile (accessed [today's date]).

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