Is DNAH3 p.Arg484His (c.1451G>A) pathogenic?

DNAH3 p.Arg484His (c.1451G>A) is classified Conflicting classifications of pathogenicity in DNAH3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-03). AlphaMissense: likely benign (0.0932); Very rare (popmax 0.008%, afr).

How common is DNAH3 p.Arg484His (c.1451G>A) in the general population?

DNAH3 p.Arg484His (c.1451G>A) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about DNAH3 p.Arg484His (c.1451G>A)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

DNAH3 p.Arg484His

c.1451G>A · VCV3774664

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.025	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -5.2
Overall
CADD	0.902	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 R513H vs ClinVar R484H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/74,990 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00266% 43/1,613,510 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
African / African-Americangrpmax	0.008%	12,498
East Asian	0.00223%	44,858
Admixed American	0.00167%	59,950
European (non-Finnish)	0.00119%	84,269
South Asian	0.0011%	90,898

Ashkenazi Jewish 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.Arg484His
Coding: c.1451G>A
MANE Select: NM_001347886
Type: single nucleotide variant
Location: chr16:21121991 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 484: the 'stem' region; a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)

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

Similar variants

DNAH3 p.Arg484Cys Uncertain significance ★ ⚠ same residue
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

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-arg484his (accessed [today's date]).

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