Is DNAH17 p.Ser4248= (c.12744G>T) pathogenic?

DNAH17 p.Ser4248= (c.12744G>T) is classified Likely benign in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Very rare (popmax 0.00224%, eas).

How common is DNAH17 p.Ser4248= (c.12744G>T) in the general population?

DNAH17 p.Ser4248= (c.12744G>T) is very rare (popmax 0.00224%, eas) (gnomAD).

DNAH17 p.Ser4248=

c.12744G>T · VCV4681999

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.1
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,720 alleles

Overall 6.87e-05% 1/1,456,456 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: DNAH17
Protein: p.Ser4248=
Coding: c.12744G>T
MANE Select: NM_173628
Type: single nucleotide variant
Location: chr17:78426953 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 4248: a UniProt-annotated variant site (in spgf39)

Full DNAH17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH17 c.7752+2T>A Pathogenic/Likely pathogenic ★★ same type
DNAH17 p.Ala1014Val Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg1217Thr Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg2941Gln Uncertain significance ★★ same type
DNAH17 p.Arg4050Gln Uncertain significance ★★ same type
DNAH17 p.Arg4101Gln Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg4246His Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg4303Cys 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/dnah17-p-ser4248 (accessed [today's date]).

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