Is ARFGAP1 p.Ser205Phe (c.614C>T) pathogenic?

ARFGAP1 p.Ser205Phe (c.614C>T) is classified Uncertain significance in ARFGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: ambiguous (0.367); Very rare (popmax 0.00127%, nfe).

How common is ARFGAP1 p.Ser205Phe (c.614C>T) in the general population?

ARFGAP1 p.Ser205Phe (c.614C>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about ARFGAP1 p.Ser205Phe (c.614C>T)?

AlphaMissense predicts ambiguous (score 0.367) — an in-silico prediction, not a clinical call.

ARFGAP1 p.Ser205Phe

c.614C>T · rs2067309030 · VCV2242998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Computational evidence

Protein change
AlphaMissense	0.367	ambiguous
REVEL	0.422	indeterminate
SaProt	LLR -13.37	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 11 kb · p 0.56 · regional, not allelic
Overall
CADD	29.5	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 0.00127% European (non-Finnish) · 15/1,180,014 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00105% 17/1,614,002 alleles · very rare exomes 17/1,461,644 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)grpmax	0.00127%	78,668

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARFGAP1
Protein: p.Ser205Phe
Coding: c.614C>T
MANE Select: NM_018209
dbSNP: rs2067309030
Type: single nucleotide variant
Location: chr20:63278982 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 61.90 · 2 PDB

Full ARFGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFGAP1 c.718-993C>T Uncertain significance ★ same type
ARFGAP1 p.Ala108Thr Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala158Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala236Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala240Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala255Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala27Thr Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala352Thr 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/arfgap1-p-ser205phe (accessed [today's date]).

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