Is DNAAF6 p.Ser18Phe (c.53C>T) pathogenic?

DNAAF6 p.Ser18Phe (c.53C>T) is classified Uncertain significance in DNAAF6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-11). AlphaMissense: likely benign (0.1001); Very rare (popmax 0.00176%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAAF6 p.Ser18Phe (c.53C>T)?

DNAAF6 p.Ser18Phe (c.53C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAAF6 p.Ser18Phe (c.53C>T) in the general population?

DNAAF6 p.Ser18Phe (c.53C>T) is very rare (popmax 0.00176%, afr) (gnomAD).

What do computational predictors say about DNAAF6 p.Ser18Phe (c.53C>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

DNAAF6 p.Ser18Phe

c.53C>T · rs1269873220 · VCV1683169

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -1.3
Regional constraint	o/e 0.86	unconstrained · MANE · 30 kb · p 0.087 · regional, not allelic
Overall
CADD	1.18	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 0.00176% African / African-American · 1/56,927 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000499% 6/1,202,550 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00176%	56,927
European (non-Finnish)	0.00056%	178,421

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: DNAAF6
Protein: p.Ser18Phe
Coding: c.53C>T
MANE Select: NM_173494
dbSNP: rs1269873220
Type: single nucleotide variant
Location: chrX:107212928 (GRCh38)
Structure: AlphaFold pLDDT 73.41
Residue 18: the 'disordered' region

Full DNAAF6 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

DNAAF6 p.Ile114Phe Uncertain significance ★★ ⚠ same condition
DNAAF6 p.Ile158Val Uncertain significance ★★ ⚠ same condition
DNAAF6 p.Ile192Asn Uncertain significance ★★ ⚠ same condition
DNAAF6 p.Ala31Thr Uncertain significance ★ ⚠ same condition
DNAAF6 p.Asn152Ile Uncertain significance ★ ⚠ same condition
DNAAF6 p.Asp87Gly Uncertain significance ★ ⚠ same condition
DNAAF6 p.Glu207Asp Uncertain significance ★ ⚠ same condition
DNAAF6 p.Glu24Lys 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/dnaaf6-p-ser18phe (accessed [today's date]).

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