Is CIMAP1C p.Arg136His (c.407G>A) pathogenic?

CIMAP1C p.Arg136His (c.407G>A) is classified Uncertain significance in CIMAP1C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely benign (0.1139); Very rare (popmax 0.00534%, afr).

How common is CIMAP1C p.Arg136His (c.407G>A) in the general population?

CIMAP1C p.Arg136His (c.407G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CIMAP1C p.Arg136His (c.407G>A)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

CIMAP1C p.Arg136His

c.407G>A · rs370869659 · VCV2493783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.56	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 5	GERP -0.99, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,337 bp · p 0.17 · regional, not allelic
Overall
CADD	19.17	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 0.00534% African / African-American · 4/74,908 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000806% 13/1,613,836 alleles · very rare exomes 9/1,461,708 · genomes 4/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,727
Remaining individualsnot grpmax-eligible	0.0032%	31,237
South Asian	0.0022%	45,542
European (non-Finnish)	0.000424%	236,001

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: CIMAP1C
Protein: p.Arg136His
Coding: c.407G>A
MANE Select: NM_175881
dbSNP: rs370869659
Type: single nucleotide variant
Location: chr15:75727122 (GRCh38)
Structure: AlphaFold pLDDT 69.94

Full CIMAP1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIMAP1C p.Ala14Glu Uncertain significance ★ ⚠ same type
CIMAP1C p.Ala226Pro Uncertain significance ★ ⚠ same type
CIMAP1C p.Ala66Asp Uncertain significance ★ ⚠ same type
CIMAP1C p.Ala66Thr Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg110His Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg146Trp Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg147His Uncertain significance ★ ⚠ same type
CIMAP1C p.Arg215Cys 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/cimap1c-p-arg136his (accessed [today's date]).

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