Is CMIP p.Asp538= (c.1614T>C) pathogenic?

CMIP p.Asp538= (c.1614T>C) is classified Likely benign in CMIP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-19). Rare (popmax 0.183%, mid); Associated with CMIP-related disorder.

What condition is associated with CMIP p.Asp538= (c.1614T>C)?

CMIP p.Asp538= (c.1614T>C) is associated with CMIP-related disorder (ClinVar).

How common is CMIP p.Asp538= (c.1614T>C) in the general population?

CMIP p.Asp538= (c.1614T>C) is rare (popmax 0.183%, mid) (gnomAD).

CMIP p.Asp538=

c.1614T>C · rs545129438 · VCV3042535

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.183%, mid)

Conditions

CMIP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -5.3
Overall
CADD	0.314	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% Middle Eastern · 11/5,996 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0796%

Overall 0.00691% 111/1,606,970 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.183%	545
Remaining individualsnot grpmax-eligible	0.0336%	2,973
Admixed American	0.0267%	3,751
European (non-Finnish)	0.005%	19,997
African / African-American	0.004%	25,018
South Asian	0.0011%	91,066

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: CMIP
Protein: p.Asp538=
Coding: c.1614T>C
MANE Select: NM_198390
dbSNP: rs545129438
Type: single nucleotide variant
Location: chr16:81696643 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.52

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

Disease context

CMIP-related disorder

Similar variants

CMIP p.Ala92Thr Uncertain significance ★ ⚠ same condition
CMIP p.Arg149Ter Uncertain significance ★ same condition
CMIP p.Glu495Lys Uncertain significance ⚠ same condition
CMIP p.Ile199Val Uncertain significance ⚠ same condition
CMIP c.1896+8C>T Likely benign same condition
CMIP c.2091+4C>T Likely benign same condition
CMIP c.2091+5G>A Benign same condition
CMIP p.Arg253= Likely benign same condition

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/cmip-p-asp538 (accessed [today's date]).

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