Is DNAH2 p.Ser2320Arg (c.6960C>A) pathogenic?

DNAH2 p.Ser2320Arg (c.6960C>A) is classified Pathogenic in DNAH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-12). AlphaMissense: likely pathogenic (0.9929); Very rare (popmax 0.00668%, eas); Associated with spermatogenic failure 45.

What condition is associated with DNAH2 p.Ser2320Arg (c.6960C>A)?

DNAH2 p.Ser2320Arg (c.6960C>A) is associated with spermatogenic failure 45 (ClinVar).

How common is DNAH2 p.Ser2320Arg (c.6960C>A) in the general population?

DNAH2 p.Ser2320Arg (c.6960C>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about DNAH2 p.Ser2320Arg (c.6960C>A)?

AlphaMissense predicts likely pathogenic (score 0.9929) — an in-silico prediction, not a clinical call.

DNAH2 p.Ser2320Arg

c.6960C>A · rs763882266 · VCV984735

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9929 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

spermatogenic failure 45

Computational evidence

Protein change
AlphaMissense	0.9929	likely pathogenic ✓ concordant with ClinVar · top 1% in DNAH2
REVEL	0.457	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.53, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 73 kb · p 9.6e-12 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000205% 3/1,461,882 alleles · very rare

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.Ser2320Arg
Coding: c.6960C>A
MANE Select: NM_020877
dbSNP: rs763882266
Type: single nucleotide variant
Location: chr17:7791976 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 2320: a UniProt-annotated variant site (in spgf45; uncertain significance; decreased protein abundance)

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

Disease context

spermatogenic failure 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same condition
DNAH2 c.12460-2A>G Likely pathogenic ★ same condition
DNAH2 c.7145+1G>A Likely pathogenic ★ same condition
DNAH2 p.Arg1924Cys Likely pathogenic ★ ⚠ same condition
DNAH2 p.Arg3882Ter Pathogenic ★ same condition
DNAH2 p.Gln1076Ter Likely pathogenic ★ same condition
DNAH2 p.Lys1273Ter Likely pathogenic ★ same condition
DNAH2 p.Trp2902Ter 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/dnah2-p-ser2320arg (accessed [today's date]).

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