Is AKTIP p.Arg139Cys (c.415C>T) pathogenic?

AKTIP p.Arg139Cys (c.415C>T) is classified Uncertain significance in AKTIP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.159); Very rare (popmax 0.00401%, afr).

How common is AKTIP p.Arg139Cys (c.415C>T) in the general population?

AKTIP p.Arg139Cys (c.415C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about AKTIP p.Arg139Cys (c.415C>T)?

AlphaMissense predicts likely benign (score 0.159) — an in-silico prediction, not a clinical call.

AKTIP p.Arg139Cys

c.415C>T · rs781311887 · VCV3108301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.159 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.159	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -12.23	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 2.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 551 bp · p 0.031 · regional, not allelic
Overall
CADD	35.0	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 0.00401% African / African-American · 3/74,866 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00335% 54/1,613,454 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,817
African / African-Americangrpmax	0.00401%	24,955
European (non-Finnish)	0.00381%	26,215
East Asian	0.00223%	44,874
Admixed American	0.00167%	59,978
South Asian	0.0011%	91,004

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg139Cys
Coding: c.415C>T
MANE Select: NM_022476
dbSNP: rs781311887
Type: single nucleotide variant
Location: chr16:53494605 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 1 PDB
Residue 139: 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.Arg13Cys Uncertain significance ★ ⚠ same type
AKTIP p.Asp205Gly Uncertain significance ★ ⚠ same type
AKTIP p.Asp247His 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-arg139cys (accessed [today's date]).

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