Is DNAH2 p.His98= (c.294T>C) pathogenic?

DNAH2 p.His98= (c.294T>C) is classified Benign in DNAH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2016-03-29). Common (popmax 17.3%, nfe) — too common for a highly-penetrant pathogenic allele.

DNAH2 p.His98=

Q: How common is DNAH2 p.His98= (c.294T>C) in the general population?

DNAH2 p.His98= (c.294T>C) is common (popmax 17.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.294T>C · rs11867551 · VCV402705

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 17.3%, nfe) — too common for a highly-penetrant pathogenic allele

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 -6.8	GERP -3.8
Overall
CADD	0.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.3% European (non-Finnish) · 203,586/1,177,614 alleles

Filtering AF 17.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.2%

Overall 15.5% 249,656/1,607,788 alleles · common exomes 228,567/1,455,620 · genomes 21,089/152,168 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	30%	3
European (non-Finnish)grpmax	17.3%	6
Finnishnot grpmax-eligible	17.3%	6
Ashkenazi Jewishnot grpmax-eligible	15.5%	6
Remaining individualsnot grpmax-eligible	14.5%	7
African / African-American	11.4%	9
Middle Eastern	10.4%	10
South Asian	8.85%	11
Admixed American	6.94%	14
East Asian	0.0404%	2,477

Amish 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: DNAH2
Protein: p.His98=
Coding: c.294T>C
MANE Select: NM_020877
dbSNP: rs11867551
Type: single nucleotide variant
Location: chr17:7727187 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 98: the 'stem' region

Full DNAH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same type
DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same type
DNAH2 p.Arg2538Gln Uncertain significance ★★ same type
DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same type
DNAH2 p.Gln2069Glu Uncertain significance ★★ same type
DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same type
DNAH2 p.Pro3819Leu Uncertain significance ★★ ⚠ same type
DNAH2 c.10169+3G>A Benign ★★ 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/dnah2-p-his98 (accessed [today's date]).

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