Is DNAH2 p.Pro815Ser (c.2443C>T) pathogenic?

DNAH2 p.Pro815Ser (c.2443C>T) is classified Conflicting classifications of pathogenicity in DNAH2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1132); Rare (popmax 0.622%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Pro815Ser (c.2443C>T)?

DNAH2 p.Pro815Ser (c.2443C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Pro815Ser (c.2443C>T) in the general population?

DNAH2 p.Pro815Ser (c.2443C>T) is rare (popmax 0.622%, nfe) (gnomAD).

What do computational predictors say about DNAH2 p.Pro815Ser (c.2443C>T)?

AlphaMissense predicts likely benign (score 0.1132) — an in-silico prediction, not a clinical call.

DNAH2 p.Pro815Ser

c.2443C>T · rs142532084 · VCV782417

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1132 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.622%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1132	likely benign
REVEL	0.023	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.025	GERP -0.55
Regional constraint	o/e 0.88	unconstrained · MANE · 73 kb · p 9.6e-12 · regional, not allelic
Overall
CADD	8.207	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 0.622% European (non-Finnish) · 7,345/1,179,950 alleles

Filtering AF 0.611% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.606%

Overall 0.507% 8,176/1,613,882 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.622%	161
Remaining individualsnot grpmax-eligible	0.435%	230
Finnishnot grpmax-eligible	0.421%	238
Admixed American	0.283%	353
African / African-American	0.101%	987
Middle Eastern	0.1%	998
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
South Asian	0.0242%	4,139

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.Pro815Ser
Coding: c.2443C>T
MANE Select: NM_020877
dbSNP: rs142532084
Type: single nucleotide variant
Location: chr17:7759119 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 815: the 'stem' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg2538Gln Uncertain significance ★★ same condition
DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same condition
DNAH2 p.Gln2069Glu Uncertain significance ★★ same condition
DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same condition
DNAH2 p.Pro3819Leu Uncertain significance ★★ ⚠ same condition
DNAH2 p.Ala1058Thr Benign/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-pro815ser (accessed [today's date]).

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