Is DNAAF5 p.Met203Val (c.607A>G) pathogenic?

DNAAF5 p.Met203Val (c.607A>G) is classified Uncertain significance in DNAAF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.2643); Very rare (popmax 0.00223%, eas); Associated with primary ciliary dyskinesia.

What condition is associated with DNAAF5 p.Met203Val (c.607A>G)?

DNAAF5 p.Met203Val (c.607A>G) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAAF5 p.Met203Val (c.607A>G) in the general population?

DNAAF5 p.Met203Val (c.607A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAAF5 p.Met203Val (c.607A>G)?

AlphaMissense predicts likely benign (score 0.2643) — an in-silico prediction, not a clinical call.

DNAAF5 p.Met203Val

c.607A>G · rs1194482161 · VCV838731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2643	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 0.33, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 59 kb · p 0.0084 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,902 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,613,686 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,902
African / African-American	0.00134%	74,900
European (non-Finnish)	0.000509%	196,654

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: DNAAF5
Protein: p.Met203Val
Coding: c.607A>G
MANE Select: NM_017802
dbSNP: rs1194482161
Type: single nucleotide variant
Location: chr7:729674 (GRCh38)
Gene constraint: LOEUF 1.12 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.80

Full DNAAF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAAF5 c.1470+1G>A Likely pathogenic ★★ same condition
DNAAF5 c.1615-2A>G Likely pathogenic ★★ same condition
DNAAF5 p.Arg253Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 p.Cys500Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
DNAAF5 p.Leu795Pro Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 p.Trp309Ter Pathogenic/Likely pathogenic ★★ same condition
DNAAF5 c.780+6T>A Uncertain significance ★★ same condition
DNAAF5 c.905+4C>T 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/dnaaf5-p-met203val (accessed [today's date]).

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