Is DNHD1 p.Ser1347Arg (c.4041C>A) pathogenic?

DNHD1 p.Ser1347Arg (c.4041C>A) is classified Conflicting classifications of pathogenicity in DNHD1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-01). AlphaMissense: likely benign (0.1811); Rare (popmax 0.105%, nfe).

How common is DNHD1 p.Ser1347Arg (c.4041C>A) in the general population?

DNHD1 p.Ser1347Arg (c.4041C>A) is rare (popmax 0.105%, nfe) (gnomAD).

What do computational predictors say about DNHD1 p.Ser1347Arg (c.4041C>A)?

AlphaMissense predicts likely benign (score 0.1811) — an in-silico prediction, not a clinical call.

DNHD1 p.Ser1347Arg

c.4041C>A · rs189772244 · VCV493088

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1811 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1811	likely benign
REVEL	0.258	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 -11	GERP -3.2
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	0.058	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 0.105% European (non-Finnish) · 1,202/1,146,982 alleles

Filtering AF 0.0999% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0978%

Overall 0.101% 1,571/1,551,718 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.377%	265
Ashkenazi Jewishnot grpmax-eligible	0.202%	494
European (non-Finnish)grpmax	0.105%	954
Remaining individualsnot grpmax-eligible	0.0765%	1,307
Admixed American	0.0627%	1,594
Middle Eastern	0.0501%	1,997
East Asian	0.00489%	20,462
African / African-American	0.00273%	36,585

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: DNHD1
Protein: p.Ser1347Arg
Coding: c.4041C>A
MANE Select: NM_144666
dbSNP: rs189772244
Type: single nucleotide variant
Location: chr11:6544980 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

Full DNHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNHD1 p.Ser1347= Benign/Likely benign ★★ same residue
DNHD1 p.Arg2928Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Glu1153Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Tyr2166Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg1582Trp Uncertain significance ★★ same type
DNHD1 p.Arg1873Ser 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/dnhd1-p-ser1347arg (accessed [today's date]).

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