Is DNAH2 p.Pro4184= (c.12552C>G) pathogenic?

DNAH2 p.Pro4184= (c.12552C>G) is classified Benign in DNAH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-01). Low-frequency (popmax 2.92%, afr); Associated with DNAH2-related disorder.

What condition is associated with DNAH2 p.Pro4184= (c.12552C>G)?

DNAH2 p.Pro4184= (c.12552C>G) is associated with DNAH2-related disorder (ClinVar).

How common is DNAH2 p.Pro4184= (c.12552C>G) in the general population?

DNAH2 p.Pro4184= (c.12552C>G) is low-frequency (popmax 2.92%, afr) (gnomAD).

DNAH2 p.Pro4184=

c.12552C>G · rs11872058 · VCV3038414

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.92%, afr)

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 -13	GERP -3.1
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.92% African / African-American · 2,190/75,030 alleles

Filtering AF 2.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.78%

Overall 0.161% 2,600/1,614,188 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.92%	34
Admixed American	0.213%	469
Remaining individualsnot grpmax-eligible	0.149%	672
Middle Eastern	0.148%	674
South Asian	0.0165%	6,072
European (non-Finnish)	0.014%	7,152

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.Pro4184=
Coding: c.12552C>G
MANE Select: NM_020877
dbSNP: rs11872058
Type: single nucleotide variant
Location: chr17:7831482 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 4184: a UniProt-annotated variant site (in spgf45; decreased protein abundance; loss of inner dynein arm assembly; in spermatozoa from patients)

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-pro4184 (accessed [today's date]).

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