Is NME8 p.Val73= (c.219G>A) pathogenic?

NME8 p.Val73= (c.219G>A) is classified Benign/Likely benign in NME8 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 15.2%, mid) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with NME8 p.Val73= (c.219G>A)?

NME8 p.Val73= (c.219G>A) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 6 (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

NME8 p.Val73=

Q: How common is NME8 p.Val73= (c.219G>A) in the general population?

NME8 p.Val73= (c.219G>A) is common (popmax 15.2%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.219G>A · rs3213976 · VCV164800

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 15.2%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss, 20 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.4	GERP -3.1, phastCons 0.025
Overall
CADD	4.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.2% Middle Eastern · 915/6,026 alleles

Filtering AF 14.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 14%

Overall 10.7% 171,783/1,608,500 alleles · common exomes 158,478/1,456,328 · genomes 13,305/152,172 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	15.2%	7
Ashkenazi Jewishnot grpmax-eligible	14.1%	7
Admixed American	12.5%	8
European (non-Finnish)	11.5%	9
Remaining individualsnot grpmax-eligible	10.7%	9
Finnishnot grpmax-eligible	8.59%	12
East Asian	8.49%	12
Amishnot grpmax-eligible	8.22%	12
South Asian	6.17%	16
African / African-American	2.47%	40

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.Val73=
Coding: c.219G>A
MANE Select: NM_016616
dbSNP: rs3213976
Type: single nucleotide variant
Location: chr7:37857294 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.81
Residue 73: the thioredoxin domain

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

Disease context

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

Also linked: primary ciliary dyskinesia 6

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-val73 (accessed [today's date]).

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