Is CIMAP1D p.Arg138Trp (c.412C>T) pathogenic?

CIMAP1D p.Arg138Trp (c.412C>T) is classified Uncertain significance in CIMAP1D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely benign (0.1386); Ultra-rare (popmax 0.0179%, afr).

How common is CIMAP1D p.Arg138Trp (c.412C>T) in the general population?

CIMAP1D p.Arg138Trp (c.412C>T) is ultra-rare (popmax 0.0179%, afr) (gnomAD).

What do computational predictors say about CIMAP1D p.Arg138Trp (c.412C>T)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

CIMAP1D p.Arg138Trp

c.412C>T · VCV4653874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.7	GERP -0.69, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.28 · regional, not allelic
Overall
CADD	23.5	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 0.0179% African / African-American · 13/72,482 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00838%

Overall 0.00233% 36/1,542,108 alleles · ultra-rare exomes 27/1,390,088 · genomes 9/152,020 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0179%	5,576
Middle Eastern	0.0171%	5,844
European (non-Finnish)	0.00183%	54,507
South Asian	0.0012%	83,384

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: CIMAP1D
Protein: p.Arg138Trp
Coding: c.412C>T
MANE Select: NM_182577
Type: single nucleotide variant
Location: chr19:464302 (GRCh38)
Structure: AlphaFold pLDDT 67.70

Full CIMAP1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1D p.Ala255Ser Uncertain significance ★ ⚠ same type
CIMAP1D p.Ala66Thr Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg101Cys Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Gln Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg11Trp Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg136His Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg148Cys Uncertain significance ★ ⚠ same type
CIMAP1D p.Arg148His 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/cimap1d-p-arg138trp (accessed [today's date]).

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