Is DNAH7 p.Val3485fs (c.10453del) pathogenic?

DNAH7 p.Val3485fs (c.10453del) is classified Likely benign in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Ultra-rare (popmax 0.0636%, nfe).

How common is DNAH7 p.Val3485fs (c.10453del) in the general population?

DNAH7 p.Val3485fs (c.10453del) is ultra-rare (popmax 0.0636%, nfe) (gnomAD).

DNAH7 p.Val3485fs

c.10453del · rs534989756 · VCV729739

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0636%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 56 of 65
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0636% European (non-Finnish) · 750/1,179,992 alleles

Filtering AF 0.0597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0582%

Overall 0.0573% 925/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.429%	233
European (non-Finnish)grpmax	0.0636%	1,573
Remaining individualsnot grpmax-eligible	0.0544%	1,839
African / African-American	0.0107%	9,382
Finnishnot grpmax-eligible	0.00625%	16,009
Admixed American	0.00333%	30,009

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: DNAH7
Protein: p.Val3485fs
Coding: c.10453del
MANE Select: NM_018897
dbSNP: rs534989756
Type: Deletion
Location: chr2:195796638 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 3485: the 'aaa 6' region

Full DNAH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH7 c.1627-11_1630del Uncertain significance ★ same type
DNAH7 p.Ile2403fs Uncertain significance ★ same type
DNAH7 p.Ile3707fs Uncertain significance ★ same type
DNAH7 p.Lys346fs Uncertain significance ★ same type
DNAH7 p.Met938fs Uncertain significance ★ same type
DNAH7 c.4549-3del Benign ★ same type
DNAH7 c.4897-8del Benign ★ same type
DNAH7 c.744-11_744-9del Likely benign 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/dnah7-p-val3485fs (accessed [today's date]).

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