Is CD177 p.Val432Ala (c.1295T>C) pathogenic?

CD177 p.Val432Ala (c.1295T>C) is classified Likely benign in CD177 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). Ultra-rare (popmax 0.0203%, nfe).

How common is CD177 p.Val432Ala (c.1295T>C) in the general population?

CD177 p.Val432Ala (c.1295T>C) is ultra-rare (popmax 0.0203%, nfe) (gnomAD).

CD177 p.Val432Ala

c.1295T>C · rs201053454 · VCV2518330

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, 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 0.41	GERP -2.4, phastCons 0.001
Regional constraint	o/e 1.18	unconstrained · MANE · 8,602 bp · p 3.2e-05 · regional, not allelic
Overall
CADD	0.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0203% European (non-Finnish) · 227/1,120,120 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.0204% 314/1,539,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.1%	998
European (non-Finnish)grpmax	0.0203%	4,934
Middle Eastern	0.0169%	5,918
Remaining individualsnot grpmax-eligible	0.0151%	6,634
South Asian	0.0102%	9,804
East Asian	0.00905%	11,050
Admixed American	0.00173%	57,706
African / African-American	0.00137%	73,108

Finnish 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.Val432Ala
Coding: c.1295T>C
MANE Select: NM_020406
dbSNP: rs201053454
Type: single nucleotide variant
Location: chr19:43362301 (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-val432ala (accessed [today's date]).

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