Is DNAH17 p.Ala700Val (c.2099C>T) pathogenic?

DNAH17 p.Ala700Val (c.2099C>T) is classified Uncertain significance in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely benign (0.2465); Ultra-rare (popmax 0.0132%, sas); Associated with Inborn genetic diseases.

What condition is associated with DNAH17 p.Ala700Val (c.2099C>T)?

DNAH17 p.Ala700Val (c.2099C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH17 p.Ala700Val (c.2099C>T) in the general population?

DNAH17 p.Ala700Val (c.2099C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about DNAH17 p.Ala700Val (c.2099C>T)?

AlphaMissense predicts likely benign (score 0.2465) — an in-silico prediction, not a clinical call.

DNAH17 p.Ala700Val

c.2099C>T · VCV3272739

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2465 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2465	likely benign
REVEL	0.401	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 0.75, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 151 kb · p 3.8e-12 · regional, not allelic
Overall
CADD	25.4	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 0.0132% South Asian · 12/90,978 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00285% 46/1,613,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,582
African / African-American	0.00934%	10,704
Admixed American	0.00667%	14,989
East Asian	0.00223%	44,896
European (non-Finnish)	0.00186%	53,625

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: DNAH17
Protein: p.Ala700Val
Coding: c.2099C>T
MANE Select: NM_173628
Type: single nucleotide variant
Location: chr17:78558187 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 700: a UniProt-annotated variant site (in spgf39); the 'stem' region

Full DNAH17 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

DNAH17 p.Ala700Glu Uncertain significance ★ same residue
DNAH17 p.Ala700= Likely benign ★ same residue
DNAH17 p.Ala1014Val Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg1217Thr Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg2941Gln Uncertain significance ★★ same condition
DNAH17 p.Arg4050Gln Uncertain significance ★★ same condition
DNAH17 p.Arg4101Gln Uncertain significance ★★ ⚠ same condition
DNAH17 p.Arg4246His Uncertain significance ★★ ⚠ 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/dnah17-p-ala700val (accessed [today's date]).

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