Is DNAH1 p.Ile2103= (c.6309C>T) pathogenic?

DNAH1 p.Ile2103= (c.6309C>T) is classified Likely benign in DNAH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). Ultra-rare (popmax 0.0167%, amr); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Ile2103= (c.6309C>T)?

DNAH1 p.Ile2103= (c.6309C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Ile2103= (c.6309C>T) in the general population?

DNAH1 p.Ile2103= (c.6309C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

DNAH1 p.Ile2103=

c.6309C>T · rs374197928 · VCV2166831

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

spermatogenic failure 18

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 -11	GERP -3.5
Overall
CADD	0.331	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,002 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00217% 35/1,613,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
South Asian	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0032%	31,232
European (non-Finnish)	0.00161%	62,100
African / African-American	0.00133%	74,934

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: DNAH1
Protein: p.Ile2103=
Coding: c.6309C>T
MANE Select: NM_015512
dbSNP: rs374197928
Type: single nucleotide variant
Location: chr3:52370527 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 2103: a UniProt-annotated variant site (in spgf18)

Full DNAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ciliary dyskinesia, primary, 37

Similar variants

DNAH1 p.Ile2103Val Uncertain significance ★ ⚠ same residue
DNAH1 c.1034-2A>G Likely pathogenic ★★ same condition
DNAH1 c.10474+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAH1 c.10968+2C>T Likely pathogenic ★★ same condition
DNAH1 c.5244+1G>A Likely pathogenic ★★ same condition
DNAH1 p.Arg1702Ter Pathogenic ★★ same condition
DNAH1 p.Arg2479Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Arg2622Ter Pathogenic/Likely 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/dnah1-p-ile2103 (accessed [today's date]).

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