Is DCAF6 p.Val600Ile (c.1798G>A) pathogenic?

DCAF6 p.Val600Ile (c.1798G>A) is classified Uncertain significance in DCAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0574%, afr).

How common is DCAF6 p.Val600Ile (c.1798G>A) in the general population?

DCAF6 p.Val600Ile (c.1798G>A) is ultra-rare (popmax 0.0574%, afr) (gnomAD).

What do computational predictors say about DCAF6 p.Val600Ile (c.1798G>A)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

DCAF6 p.Val600Ile

c.1798G>A · rs147870716 · VCV2358757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP -1.9, phastCons 0.012
Regional constraint	o/e 0.88	unconstrained · MANE · 63 kb · p 0.0024 · regional, not allelic
Overall
CADD	14.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V523I vs ClinVar V600I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0574% African / African-American · 43/74,942 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.039%

Overall 0.00446% 72/1,612,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,743
Middle Eastern	0.0165%	6,058
Admixed American	0.00501%	19,948
Remaining individualsnot grpmax-eligible	0.0048%	20,822
East Asian	0.00446%	22,425
South Asian	0.0022%	45,460
European (non-Finnish)	0.00153%	65,517

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: DCAF6
Protein: p.Val600Ile
Coding: c.1798G>A
MANE Select: NM_001198956
dbSNP: rs147870716
Type: single nucleotide variant
Location: chr1:168043095 (GRCh38)
Gene constraint: LOEUF 0.567 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 64.23 · 1 PDB
Residue 600: the 'disordered' region

Full DCAF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCAF6 p.Thr644Ile Benign ★★ same type
ADCY10 c.292+6G>A Uncertain significance ★ same type
ADCY10 p.Gln283His Uncertain significance ★ ⚠ same type
ADCY10 p.Glu7Val Uncertain significance ★ ⚠ same type
ADCY10 p.Met237Thr Uncertain significance ★ ⚠ same type
ADCY10 p.Thr235Ser Uncertain significance ★ ⚠ same type
ADCY10 p.Thr254Met Conflicting classifications of pathogenicity ★ ⚠ same type
DCAF6 p.Ala295Val 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/dcaf6-p-val600ile (accessed [today's date]).

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