Is CDIPT p.Arg138Lys (c.413G>A) pathogenic?

CDIPT p.Arg138Lys (c.413G>A) is classified Uncertain significance in CDIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.2258); Ultra-rare (popmax 0.0134%, amr).

How common is CDIPT p.Arg138Lys (c.413G>A) in the general population?

CDIPT p.Arg138Lys (c.413G>A) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about CDIPT p.Arg138Lys (c.413G>A)?

AlphaMissense predicts likely benign (score 0.2258) — an in-silico prediction, not a clinical call.

CDIPT p.Arg138Lys

c.413G>A · rs779675840 · VCV2510207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2258 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2258	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.83	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 2.7	GERP -0.016, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 3,665 bp · p 0.068 · regional, not allelic
Overall
CADD	15.97	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 0.0134% Admixed American · 8/59,872 alleles

Filtering AF 0.00663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000936% 15/1,602,780 alleles · ultra-rare exomes 10/1,450,568 · genomes 5/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,484
East Asian	0.00669%	14,941
Remaining individualsnot grpmax-eligible	0.00161%	62,106
European (non-Finnish)	0.000256%	390,035

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: CDIPT
Protein: p.Arg138Lys
Coding: c.413G>A
MANE Select: NM_006319
dbSNP: rs779675840
Type: single nucleotide variant
Location: chr16:29860582 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.02

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

Similar variants

CDIPT p.Ala140Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala146Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala206Val Uncertain significance ★ ⚠ same type
CDIPT p.Ala22Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala48Thr Uncertain significance ★ same type
CDIPT p.Ala84Val Uncertain significance ★ ⚠ same type
CDIPT p.Arg115Gln Uncertain significance ★ ⚠ same type
CDIPT p.Arg173Trp 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/cdipt-p-arg138lys (accessed [today's date]).

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