Is ADHFE1 p.Arg6Gln (c.17G>A) pathogenic?

ADHFE1 p.Arg6Gln (c.17G>A) is classified Uncertain significance in ADHFE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: ambiguous (0.4374); Absent from gnomAD v4.1.

How common is ADHFE1 p.Arg6Gln (c.17G>A) in the general population?

ADHFE1 p.Arg6Gln (c.17G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADHFE1 p.Arg6Gln (c.17G>A)?

AlphaMissense predicts ambiguous (score 0.4374) — an in-silico prediction, not a clinical call.

ADHFE1 p.Arg6Gln

c.17G>A · VCV3273142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4374 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,360,138)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4374	ambiguous
REVEL	0.114	moderately benign-leaning
SaProt	LLR -8.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -1.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 36 kb · p 0.69 · regional, not allelic
Overall
CADD	20.4	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

No allele count reported in gnomAD v4.1 (AN 1,360,138). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADHFE1
Protein: p.Arg6Gln
Coding: c.17G>A
MANE Select: NM_144650
Type: single nucleotide variant
Location: chr8:66432533 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.00

Full ADHFE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADHFE1 p.Ala136Asp Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala233Thr Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala237Thr Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala247Ser Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala271Glu Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala283Ser Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala283Val Uncertain significance ★ ⚠ same type
ADHFE1 p.Ala286Glu 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/adhfe1-p-arg6gln (accessed [today's date]).

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