Is ADGRF1 p.Ser96Arg (c.288C>G) pathogenic?

ADGRF1 p.Ser96Arg (c.288C>G) is classified Benign in ADGRF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-08). AlphaMissense: likely benign (0.1054); Low-frequency (popmax 2.41%, afr).

How common is ADGRF1 p.Ser96Arg (c.288C>G) in the general population?

ADGRF1 p.Ser96Arg (c.288C>G) is low-frequency (popmax 2.41%, afr) (gnomAD).

What do computational predictors say about ADGRF1 p.Ser96Arg (c.288C>G)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

ADGRF1 p.Ser96Arg

c.288C>G · rs74832476 · VCV785174

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.41%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -2.2, phastCons 0.015
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.0052 · regional, not allelic
Overall
CADD	12.62	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 2.41% African / African-American · 1,809/75,014 alleles

Filtering AF 2.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.28%

Overall 0.126% 2,030/1,613,330 alleles · low-frequency exomes 977/1,461,016 · genomes 1,053/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.41%	41
Admixed American	0.162%	618
Remaining individualsnot grpmax-eligible	0.141%	710
Middle Eastern	0.0828%	1,208
South Asian	0.0033%	30,337
European (non-Finnish)	0.00237%	42,123

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: ADGRF1
Protein: p.Ser96Arg
Coding: c.288C>G
MANE Select: NM_153840
dbSNP: rs74832476
Type: single nucleotide variant
Location: chr6:47024207 (GRCh38)
Gene constraint: LOEUF 1.247 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.05 · 10 PDB

Full ADGRF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRF1 p.Thr803Pro Benign/Likely benign ★★ ⚠ same type
ADGRF1 p.Ala178Val Uncertain significance ★ ⚠ same type
ADGRF1 p.Ala378Val Uncertain significance ★ ⚠ same type
ADGRF1 p.Ala784Thr Uncertain significance ★ ⚠ same type
ADGRF1 p.Arg161Ser Uncertain significance ★ ⚠ same type
ADGRF1 p.Arg395Trp Uncertain significance ★ ⚠ same type
ADGRF1 p.Arg403Leu Uncertain significance ★ ⚠ same type
ADGRF1 p.Arg403Pro 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/adgrf1-p-ser96arg (accessed [today's date]).

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