Is DNAH3 p.Arg862Ser (c.2586G>C) pathogenic?

DNAH3 p.Arg862Ser (c.2586G>C) is classified Likely benign in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely pathogenic (0.9411); Rare (popmax 0.797%, nfe).

How common is DNAH3 p.Arg862Ser (c.2586G>C) in the general population?

DNAH3 p.Arg862Ser (c.2586G>C) is rare (popmax 0.797%, nfe) (gnomAD).

What do computational predictors say about DNAH3 p.Arg862Ser (c.2586G>C)?

AlphaMissense predicts likely pathogenic (score 0.9411) — an in-silico prediction, not a clinical call.

DNAH3 p.Arg862Ser

c.2586G>C · rs117470111 · VCV2646301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9411 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.797%, nfe)

Computational evidence

Protein change
AlphaMissense	0.9411	likely pathogenic
REVEL	0.4	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP -1, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R908S vs ClinVar R862S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.797% European (non-Finnish) · 9,402/1,179,988 alleles

Filtering AF 0.783% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.778%

Overall 0.712% 11,498/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.43%	70
Ashkenazi Jewishnot grpmax-eligible	1.31%	76
European (non-Finnish)grpmax	0.797%	126
Remaining individualsnot grpmax-eligible	0.621%	161
Admixed American	0.413%	242
Middle Eastern	0.248%	404
Amishnot grpmax-eligible	0.219%	456
African / African-American	0.147%	682
South Asian	0.0318%	3,141

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DNAH3
Protein: p.Arg862Ser
Coding: c.2586G>C
MANE Select: NM_001347886
dbSNP: rs117470111
Type: single nucleotide variant
Location: chr16:21087002 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 862: the 'stem' region

Full DNAH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
DNAH3 p.Arg1228Gln Uncertain significance ★★ same type
DNAH3 p.Arg635Gln Uncertain significance ★★ same type
DNAH3 p.Asn1728Ser Uncertain significance ★★ ⚠ same type
DNAH3 p.Asp3656Asn Uncertain significance ★★ same type
DNAH3 p.Leu2597Val Uncertain significance ★★ same type
DNAH3 p.Leu4044Phe Uncertain significance ★★ ⚠ same type
DNAH3 p.Lys374Gln Uncertain significance ★★ ⚠ same type

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/dnah3-p-arg862ser (accessed [today's date]).

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