Is CD177 p.Pro318= (c.954T>C) pathogenic?

CD177 p.Pro318= (c.954T>C) is classified Likely benign in CD177 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Very rare (popmax 0.000172%, nfe).

How common is CD177 p.Pro318= (c.954T>C) in the general population?

CD177 p.Pro318= (c.954T>C) is very rare (popmax 0.000172%, nfe) (gnomAD).

CD177 p.Pro318=

c.954T>C · rs2513513282 · VCV2650062

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

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 -1.7	GERP -2.6
Overall
CADD	2.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,162,270 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000139% 2/1,434,522 alleles · very rare

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.Pro318=
Coding: c.954T>C
MANE Select: NM_020406
dbSNP: rs2513513282
Type: single nucleotide variant
Location: chr19:43361452 (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-pro318 (accessed [today's date]).

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