Is NME8 p.Phe86= (c.258T>C) pathogenic?

NME8 p.Phe86= (c.258T>C) is classified Likely benign in NME8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-19). Very rare (popmax 0.00255%, nfe); Associated with primary ciliary dyskinesia 6.

What condition is associated with NME8 p.Phe86= (c.258T>C)?

NME8 p.Phe86= (c.258T>C) is associated with primary ciliary dyskinesia 6 (ClinVar).

How common is NME8 p.Phe86= (c.258T>C) in the general population?

NME8 p.Phe86= (c.258T>C) is very rare (popmax 0.00255%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NME8 p.Phe86=

c.258T>C · rs775554270 · VCV2195652

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00255%, nfe)

Conditions

primary ciliary dyskinesia 6

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 0.19	GERP -2.1, phastCons 0.99
Overall
CADD	8.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00255% European (non-Finnish) · 30/1,174,938 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00193% 31/1,607,776 alleles · very rare exomes 28/1,455,564 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00255%	39,165
Remaining individualsnot grpmax-eligible	0.00161%	62,242

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: NME8
Protein: p.Phe86=
Coding: c.258T>C
MANE Select: NM_016616
dbSNP: rs775554270
Type: single nucleotide variant
Location: chr7:37857333 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.81
Residue 86: the thioredoxin domain

Full NME8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

NME8 c.1139+3A>G Uncertain significance ★★ same condition
NME8 c.454+1G>A Uncertain significance ★★ same condition
NME8 p.Ala122Gly Uncertain significance ★★ ⚠ same condition
NME8 p.Ala440Asp Uncertain significance ★★ ⚠ same condition
NME8 p.Ala530Val Uncertain significance ★★ ⚠ same condition
NME8 p.Ala69Gly Uncertain significance ★★ ⚠ same condition
NME8 p.Arg127Gln Uncertain significance ★★ ⚠ same condition
NME8 p.Arg203Gln 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/nme8-p-phe86 (accessed [today's date]).

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