Is NCF2 p.Pro296Gln (c.887C>A) pathogenic?

NCF2 p.Pro296Gln (c.887C>A) is classified Uncertain significance in NCF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.3066); Very rare (popmax 0.00445%, eas); Associated with Inborn genetic diseases.

What condition is associated with NCF2 p.Pro296Gln (c.887C>A)?

NCF2 p.Pro296Gln (c.887C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NCF2 p.Pro296Gln (c.887C>A) in the general population?

NCF2 p.Pro296Gln (c.887C>A) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about NCF2 p.Pro296Gln (c.887C>A)?

AlphaMissense predicts likely benign (score 0.3066) — an in-silico prediction, not a clinical call.

NCF2 p.Pro296Gln

c.887C>A · rs549428558 · VCV2543279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3066	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 34 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,904 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,052 alleles · very rare exomes 1/1,461,860 · genomes 1/152,192 · joint denominator

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: NCF2
Protein: p.Pro296Gln
Coding: c.887C>A
MANE Select: NM_000433
dbSNP: rs549428558
Type: single nucleotide variant
Location: chr1:183566957 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 7 PDB
Residue 296: the sh3 1 domain; a β-strand

Full NCF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCF2 p.Ala17Thr Uncertain significance ★★ ⚠ same condition
NCF2 p.Arg38Trp Uncertain significance ★★ ⚠ same condition
NCF2 p.Arg397Gln Uncertain significance ★★ ⚠ same condition
NCF2 p.Arg397Trp Uncertain significance ★★ ⚠ same condition
NCF2 p.Asp412Glu Uncertain significance ★★ ⚠ same condition
NCF2 p.Asp446Tyr Uncertain significance ★★ ⚠ same condition
NCF2 p.Pro320Ala Uncertain significance ★★ ⚠ same condition
NCF2 p.Pro351Leu Uncertain significance ★★ ⚠ 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/ncf2-p-pro296gln (accessed [today's date]).

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