Is DNAH2 p.Ala989= (c.2967C>T) pathogenic?

DNAH2 p.Ala989= (c.2967C>T) is classified Benign in DNAH2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-12-05). Common (popmax 9.58%, mid) — too common for a highly-penetrant pathogenic allele; Associated with DNAH2-related disorder.

What condition is associated with DNAH2 p.Ala989= (c.2967C>T)?

DNAH2 p.Ala989= (c.2967C>T) is associated with DNAH2-related disorder (ClinVar).

DNAH2 p.Ala989=

Q: How common is DNAH2 p.Ala989= (c.2967C>T) in the general population?

DNAH2 p.Ala989= (c.2967C>T) is common (popmax 9.58%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2967C>T · rs12185237 · VCV3056427

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.58%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

DNAH2-related disorder

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 -10	GERP -3.3
Overall
CADD	0.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.58% Middle Eastern · 580/6,052 alleles

Filtering AF 8.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.68%

Overall 4.4% 70,956/1,613,886 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	9.58%	10
South Asian	7.06%	14
European (non-Finnish)	4.79%	21
Remaining individualsnot grpmax-eligible	4.24%	24
Ashkenazi Jewishnot grpmax-eligible	3.31%	30
Finnishnot grpmax-eligible	2.68%	37
Admixed American	2.47%	40
Amishnot grpmax-eligible	2.41%	41
African / African-American	0.74%	135
East Asian	0.111%	898

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.Ala989=
Coding: c.2967C>T
MANE Select: NM_020877
dbSNP: rs12185237
Type: single nucleotide variant
Location: chr17:7760921 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 989: the 'stem' region

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

Disease context

DNAH2-related disorder

Similar variants

DNAH2 p.Arg1633Gly Uncertain significance ⚠ same condition
DNAH2 c.11478+4G>A Benign same condition
DNAH2 c.1171-715G>A Likely benign same condition
DNAH2 c.1377-9C>A Likely benign same condition
DNAH2 c.1904+123T>C Benign same condition
DNAH2 c.1904+136C>T Likely benign same condition
DNAH2 c.1904+345A>G Likely benign same condition
DNAH2 c.3179+4C>T Likely benign 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/dnah2-p-ala989 (accessed [today's date]).

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