Is DNAH8 p.Arg242His (c.725G>A) pathogenic?

DNAH8 p.Arg242His (c.725G>A) is classified Conflicting classifications of pathogenicity in DNAH8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.0892); Rare (popmax 0.261%, eas); Associated with spermatogenic failure 46.

What condition is associated with DNAH8 p.Arg242His (c.725G>A)?

DNAH8 p.Arg242His (c.725G>A) is associated with spermatogenic failure 46, primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Arg242His (c.725G>A) in the general population?

DNAH8 p.Arg242His (c.725G>A) is rare (popmax 0.261%, eas) (gnomAD).

What do computational predictors say about DNAH8 p.Arg242His (c.725G>A)?

AlphaMissense predicts likely benign (score 0.0892) — an in-silico prediction, not a clinical call.

DNAH8 p.Arg242His

c.725G>A · rs142863013 · VCV238655

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0892 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.261%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

spermatogenic failure 46

Computational evidence

Protein change
AlphaMissense	0.0892	likely benign
REVEL	0.095	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -5.5
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.008 · regional, not allelic
Overall
CADD	13.23	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R25H vs ClinVar R242H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.261% East Asian · 117/44,844 alleles

Filtering AF 0.222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.208%

Overall 0.0294% 474/1,613,482 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.261%	383
Remaining individualsnot grpmax-eligible	0.0897%	1,115
African / African-American	0.032%	3,125
European (non-Finnish)	0.0224%	4,469
South Asian	0.00879%	11,380
Admixed American	0.00667%	14,994
Finnishnot grpmax-eligible	0.00156%	64,016

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: DNAH8
Protein: p.Arg242His
Coding: c.725G>A
MANE Select: NM_001206927
dbSNP: rs142863013
Type: single nucleotide variant
Location: chr6:38734588 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)

Full DNAH8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 46 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

Similar variants

DNAH8 p.Arg242Cys Benign ★ same residue
DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg2878Ter Pathogenic ★★ 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/dnah8-p-arg242his (accessed [today's date]).

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