Is CD177 p.Pro44Ser (c.130C>T) pathogenic?

CD177 p.Pro44Ser (c.130C>T) is classified Uncertain significance in CD177 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). Very rare (popmax 8.48e-05%, nfe).

How common is CD177 p.Pro44Ser (c.130C>T) in the general population?

CD177 p.Pro44Ser (c.130C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CD177 p.Pro44Ser

c.130C>T · VCV4222604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.2	GERP -2.8
Regional constraint	o/e 1.18	unconstrained · MANE · 8,602 bp · p 3.2e-05 · regional, not allelic
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,852 alleles

Overall 0.000124% 2/1,613,760 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,456
European (non-Finnish)grpmax	8.48e-05%	1,179,852

Remaining individuals 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: CD177
Protein: p.Pro44Ser
Coding: c.130C>T
MANE Select: NM_020406
Type: single nucleotide variant
Location: chr19:43353930 (GRCh38)
Gene constraint: LOEUF 1.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.67 · 2 PDB

Full CD177 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD177 p.Gly431Arg Benign ★★ same type
CD177 p.Lys366Arg Benign ★★ same type
CD177 p.Phe208Val Benign ★★ same type
CD177 p.Ser364Thr Benign ★★ same type
CD177 p.Thr210Ile Benign/Likely benign ★★ same type
CD177 p.Ala281Asp Uncertain significance ★ same type
CD177 p.Ala3Val Uncertain significance ★ same type
CD177 p.Ala425Pro 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/cd177-p-pro44ser (accessed [today's date]).

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