Is CMIP p.Val547= (c.1641G>A) pathogenic?

CMIP p.Val547= (c.1641G>A) is classified Benign in CMIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.347%, mid).

How common is CMIP p.Val547= (c.1641G>A) in the general population?

CMIP p.Val547= (c.1641G>A) is rare (popmax 0.347%, mid) (gnomAD).

CMIP p.Val547=

c.1641G>A · rs183876152 · VCV717038

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.347%, mid)

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 6.5	GERP 2.6, phastCons 1
Overall
CADD	14.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.347% Middle Eastern · 21/6,052 alleles

Filtering AF 0.268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.21% 3,371/1,608,386 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	6.14%	16
Middle Easterngrpmax	0.347%	288
Admixed American	0.304%	329
Remaining individualsnot grpmax-eligible	0.244%	410
European (non-Finnish)	0.234%	426
South Asian	0.129%	776
Finnishnot grpmax-eligible	0.0689%	1,452
African / African-American	0.0561%	1,784
East Asian	0.00223%	44,808

Amish 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: CMIP
Protein: p.Val547=
Coding: c.1641G>A
MANE Select: NM_198390
dbSNP: rs183876152
Type: single nucleotide variant
Location: chr16:81699687 (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

Similar variants

CMIP c.1638+10G>A Likely benign ★★ same type
CMIP c.2269-10C>T Benign/Likely benign ★★ same type
CMIP p.Asn295= Benign ★★ same type
CMIP p.Leu369= Likely benign ★★ same type
CMIP p.Pro414= Benign ★★ same type
CMIP c.1035-1G>A Uncertain significance ★ same type
CMIP p.Ala113Thr Uncertain significance ★ ⚠ same type
CMIP p.Ala299Thr 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/cmip-p-val547 (accessed [today's date]).

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